Worldwide Regulatory Strategy
Placement in EU Regulatory Policy
Pfizer
Edward Cooper
University of Bath
September 2011-August 2012
Course: BSc Biochemistry with Professional Placement
Company: Pfizer
Department: WRS EU Regulatory Policy
Supervisor: Nick Sykes
EU Regulatory Policy at Pfizer Placement Report
Table of Contents
1. Executive Summary
2. Introduction
a. History of Pfizer
b. Corporate Initiatives and the Future of Pfizer
c. Pfizer in Numbers
d. Pfizer at Discovery Park, Sandwich
3. Product Lifecycle and Regulatory Affairs
a. Product Development and Lifecycle
b. Regulatory Authorities
i. European Medicines Agency
ii. National Competent Authorities
iii. Non-EU Regulatory Authorities
c. Regulatory Procedures in the EU
4. Worldwide Safety and Regulatory at Pfizer
a. Organisation Structure
b. Department Roles and Responsibilities
5. Regulatory Policy
a. Regulatory and Policy Environment 2011-2012
b. Legislation and Guidances in the EU
c. Trade associations and Policy Interactions
d. Regulatory Policy at Pfizer
6. Personal Activities and Responsibilities
a. Key Topic Areas
i. Article 57(2) of Pharmacovigilance Directive
ii. Paediatrics
iii. Biosimilars
iv. Others
b. Other Activities and Responsibilities
7. Placement Evaluation
8. Appendices
a. Acronyms
b. Annex I – Key Documents and Terminologies
c. Annex II – Annexed Resources
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Executive Summary
Introduction
2a. History of Pfizer
Pfizer was founded by Charles Pfizer and Charles Ehart in 1849 in Brooklyn, New York as a finechemicals business. The first product was a palatable form of santonin, an antiparasitic used to treat
intestinal worms which were endemic in at the time in America. In the 1860s Pfizers growth is
carried by providing supplies of drugs for the Union Army as demand soars. Other early products
included tartaric acid and cream of tartar, both of which were vital to the food and chemical
industries.
In 1880 Pfizer began manufacturing citric acid and soon became America’s leading producer. This
coincided with a growth in popularity for new carbonated drinks increasing demand for citric acid. It
became Pfizer’s most profitable product, spurring developments such as mould and later deep tank
fermentation, and formed the economic basis for the growth to follow.
In the 1930s and 40s the development focus was on the production of vitamins. That was until in
1941 Pfizer responded to an appeal from the United States Government to expedite the
manufacture of penicillin to treat allied soldiers fighting in World War 2. Pfizer was the only
company to use deep tank fermentation for its production, a huge capital risk for the company
which came good providing a means to produce much greater quantities of penicillin.
Terramycin® (oxytetracycline), a broad-spectrum antibiotic is Pfizer’s first innovative pharmaceutical
and the product of the company’s first discovery program. It is first sold under the Pfizer label in the
US in 1950. It is also at this time that Pfizer began expansion into overseas markets with operations
starting in Belgium, Brazil, Canada, Cuba, England, Mexico, Panama and Peurto Rico.
Pfizer’s Research and Development (R&D) facility at Sandwich, Kent was first opened in 1954. It was
partly driven by a requirement to circumvent the bulk importation restrictions placed on medical
materials not fully manufactured in the UK imposed by the government at that time. The site grew
throughout the 1950s as Pfizer’s portfolio continued to expand. By 1960 Pfzier Ltd employed over
2,000 staff at the Sandwich site.
In 1972 Pfizer crosses the billion-dollar sales threshold. Recognizing that the key to Pfizer's
future growth lies in its ability to discover and develop innovative pharmaceuticals, Chairman
Ed Pratt increases the company's Research and Development budget from about 5 percent to
15 to 20 percent of sales. He also leads the ongoing battle for intellectual property protection
worldwide to encourage and safeguard innovation.
By early 1992 Pfizer had brought more new products to the market in a three year period than any
other pharmaceutical company in Britain. Pfizer’s success in discovering new drugs continued
throughout the 1990s with several of its best selling and most well known products such as Diflucan
and Viagra (which was discovered in the Sandwich laboratories) coming to the market in this period.
In 2000 Pfizer acquired Warner-Lambert to make it the world’s fastest growing pharmaceutical
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company. In 2009 Pfizer announced its plans to acquire Wyeth in a bid to strengthen its biologics
and vaccines sectors.
In February 2011 Pfizer announced its planned closure of its European R&D headquarters at
Sandwich, UK. The aim was to address the profit shortfall resulting from heavy research expenditure
failing to stimulate sufficient new products. In the time since Pfizer has continued to streamline its
R&D enterprise worldwide in a bid to increase productivity based on more focused areas of
research. (1) (2)
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2b. Corporate Initiatives and the Future of Pfizer
At present the pharmaceutical Industry is operating in the hardest climate it has known. With the
famed “Patent Cliff” approaching and an estimated x% of blockbuster drugs loosing exclusivity in the
major markets by 2015(?14) and evidence showing lower numbers of new drug approvals in recent
years than ever before Pharma is feeling the pinch.
Figure 1: Number of US FDA New Molecular Entity Approvals against R&D Spend over time.
The funding demographic is changing too with new pressures from cost containment schemes as
well as shareholders. Whilst the ageing baby boom generation is providing plentiful demand for
products, crippling economies are straining to pay for it. There is therefore a realisation that the
Industry needs to adapt and reinvent itself.
The Mission and Vision of Pfizer
Mission Statement
“To ensure we can continue to deliver on our commitments to the patients, customers and
shareholders who rely on us, we are focused on improving the way we do business; on operating
with transparency in everything we do; and on listening to the views of all of the people involved in
health care decisions. Through working in partnership with everyone from patients to health care
providers and managed care organizations to world governments and non-governmental
organizations, our goal is to ensure that people everywhere have access to innovative treatments
and quality health care.”
Pfizer.com/About/
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Pfizer is committed to the innovative pharmaceutical model, providing prescription medicines to
patients. The overarching strategies outlined below are designed to promote the business’
continued success.
The 4 Imperatives
Designed to reflect Pfizer’s core values the key imperatives are CEO Ian Read’s communicated
drivers for ongoing success as an innovative healthcare company.
1. Fix our innovative core – Generate medicines that profoundly impact health.
Expresses the need to create a sustainable platform for growth through innovation focusing
on disease areas in which Pfizer can ‘win’. Also provides an emphasis upon the importance
of generating a greater return on investment.
2. Make the right capital allocation decisions that will maximize value for Pfizer and that create
enhanced shareholder return.
3. Be respected by society
The imperative focuses on closing the perception gap between how the company acts and
how the public believes the company acts.
4. Creating an Ownership Culture – OWN IT
The aim is to create an environment where colleagues are encouraged to take the initiative
and be accountable for the consequences, driving entrepreneurial behaviour.
Figure 2: OWN IT visual sourced from: http://world.pfizer.com/OwnIt/Pages/OWNIT.aspx
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The Three Horizons
The Worldwide Research and Development (WRD), one division within the current Pfizer
organisation, Journey to the Three Horizons strategy underpins the First Imperative; Fixing the
Innovative Core.
Horizon 1: Deliver the Portfolio
Horizon 2: Innovate new capabilities
Horizon 3: R&D Ecosystem of the Future
In a landscape where payors1 are increasingly becoming less willing to reward incremental
improvements in therapy Pfizer’s WRD organisation is focusing its efforts on projects that will
provide clear improvement in treatment options for patients. This not only means investing in assets
for areas of unmet clinical need; for Pfizer it means shifting the development paradigm towards
areas such as Precision Medicine, advanced therapeutics and biosimilars.
Pfizer is pioneering the Precision Medicine approach which targets small subsets of patients with
certain characteristics aiming to achieve enhanced results. Pfizer has already gained approval for
Crizotinib, trade named Xalkori, in the US where it is now available to patients. Crizotinib is a very
effective treatment of non-small cell lung cancer (NSCLC) for Alk+ patients; that is only patients with
a certain genotype (~5% of NSCLC patients diagnosed) which is determined through an
accompanying diagnostic test. Under the Three Horizons Strategy, Mikael Dolsten, President WRD,
has set ambitious targets for precision medicine development and expects that by 2020 4 out of
every 5 products launched will be a precision medicine drug.
1
Payors are the organisations which fund the reimbursement to companies for the medicines they provide. In
Europe this is generally state funded, for example in the UK NICE (National Institute for health and Clinical
Excellence) pays for medicines used by the NHS excluding cost covered by prescription fee.
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2c. Pfizer in Numbers
Pfizer is the world’s largest pharmaceutical by sales volume and employs in excess of 110,000 people
worldwide.
Pfizer is performing well on the stock market despite loss of exclusivity in most major markets for
Lipitor, the best selling branded medicine in history. This has however taken a clear effect upon net
sales which have been down approximately 9% in the year to date compared to 2011.
Figure 3: Pfizer Stock Price Performance Jan-Jul 31st 2012 in comparison to DRG (Pharmaceutical Index) and S&P index (500
top publically traded American Companies)
Source: One Pfizer Quarterly Update Broadcast
Figure 3 shows the Pfizer stock price at 24.04, a 4 year high on July 31st when Pfizer reported its Q2
2012 earnings.
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Figure 4: Q2 Income Statement Highlights and Demonstration of Growth in Emerging Markets
Source: One Pfizer Quarterly Update Broadcast
The negative effect of decreasing sales and foreign exchange rates2 has been to some extent offset
by aggressive share-repurchasing3. Pfizer also experienced growth in the ‘emerging markets’ which
helped to balance figures. This growth is lead by established products, branded or non-branded
generic off patent medicines which Pfizer operates based on an opportunistic basis. The reduction of
outgoings across the business through operational excellence initiatives has also been important in
turning over positive figures. Pfizer was able to reaffirm projected earnings at the end of Q2 which is
considered a strong result in this economic climate. Such reliable estimations improve investor
confidence and as a result drive the share price.
2d. Pfizer at Discovery Park, Sandwich
In February 2011 Pfizer announced a full exit from its European R&D headquarters at the Sandwich
Site. The closure and implicated job losses are of significant impact to the surrounding communities
and economic climate of East Kent.
The original decision has been reverted to some degree with Pfizer maintaining a go-forward
presence at the Sandwich site centred on the Pharmaceutical Sciences facilities. Currently there are
approximately 700 employees on the site and the expectation is that these positions will be
maintained. Pfizer is looking to sell the site and rent buildings 530, 510 and the Pilot Plant where
operations are continuing. The site has been designated as an enterprise zone, providing preferential
rates to business moving to the site.
Building 530 is now a facility shared with other companies; Mylan and Peakdale have some of the
larger footprints of the other occupants. Several spin-off companies have been incorporated into the
building.
2
Exchange rate of strong dollar working against Pfizer as a US reporting company due to revenues achieved
outside the USA, particularly in Europe, being cut when converted to US $.
3
As Pfizer buys back shares in the company it decreases the proportion of revenue that must be provided to
shareholders resulting in Pfizer earning more for each $ of revenue.
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Product Lifecycle and Regulatory Affairs
3a. Product Development and Lifecycle
Medicines are the end product of a development program which can typically take as long as 15
years. Before a medicine can be marketed for use in humans it must be shown to safe and
efficacious4 and that it can be manufactured to a high quality. There is therefore a journey from the
discovery of the active product5 through pre-clinical, non-clinical and clinical6 development to
regulatory evaluation and ongoing pharmacovigilance assessment.
The Research Phase
The productivity gap where increased R&D spend has not produced more blockbuster medicines (2b)
has lead to companies reassessing their research models. The trend has been cost cutting and
outsourcing of early stage research combined with the in-licensing of promising candidate
molecules. In effect big pharma is opting to buy in the research conducted in smaller biotech
enterprises or conducted in partnership with the academic community. The later stage development
of medicines is also being undertaken through partnerships more frequently, with the marketing
rights for the product split post approval.
Regulatory Assessment
The data generated from the 3 major data packages (quality, non-clinical and clinical) is critically
assessed by regulatory authorities to establish whether the products quality, efficacy and safety
profiles are acceptable and that any packaging and product claims are accurate relevant to available
data (3). This review is fairly complex and centres on a determination of whether the product shows
a positive benefit: risk balance. If a product is deemed to have a positive benefit : risk balance it is
usually provided with a marketing authorisation, allowing it to be used to treat patients outside of
the clinical trial setting.
Pharmacovigilance and Post Marketing Commitments
All medicinal products are subject to pharmacovigilance7 monitoring to extend knowledge beyond
clinical trial data which is limited by population size and a controlled treatment environment.
Through extensive reporting systems unwanted side effects of medicines are recorded and analysed.
This takes advantage of the huge wealth of information available in the form of real world data to
update the safety profile of medicines. This provides the data required to support the introduction
and publication of new special warnings, precautions for use and in extreme cases product
suspension or withdrawal.
4
Efficacious is defined as capable of having the desired effect, therefore in medicines efficacy is an ability to
treat or prevent a disease (or halt disease progression).
5
Active product or active product ingredient (API) is the chemical entity within the pharmaceutical product
which interacts with biological systems to stimulate the desired effect.
6
Pre-clinical is in-vitro research, Non-clinical is in-vivo (most commonly rodents) and clinical is in human.
7
Pharmacovigilance (PhV) is the practice of interpreting, understanding and preventing the occurrence of
adverse events (typically side effects of medicines).
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Post marketing commitments (PMCs) are agreed in the medicines marketing authorisation (MA) and
represent studies and evaluations the sponsor is obliged to complete following authorisation. These
typically include long term safety studies and deferred8 or longer term paediatric studies.
Post Approval Product Development
Pharmaceutical products are often further developed once authorised. This may include research
into the products use to treat different conditions or provide a different means of administering the
product. In these instances additional relevant data must be generated in a similar fashion to the
original application for MA to prove safety and efficacy. Such applications are able to draw upon the
conclusions of data previously generated where consistent.
Once available on the market more information will be learnt about the product. This may require a
change to the information available to patients and prescribers or kept in competent authority9
records. Such information is updated in real time as change signals are recognised. Medicinal
products licenses are also subject to renewal, encompassing a scientific review, on a cycle (typically
annually) which may trigger the implementation of such changes.
Loss of Exclusivity (LOE)
The loss of exclusivity represents the last major milestone in an innovative pharmaceutical lifecycle.
This is the point when other manufacturers can market copycat drugs, known as generics. Generics
are licensed on a greatly reduced data package with a requirement to show that they are “essentially
similar” to the reference product. Generics can therefore be sold at significantly cut prices requiring
the innovator company to produce strategies to maintain the greatest possible market share.
8
Studies in children can in some cases be deferred until after adult development to prevent a lack of paediatric
data delaying availability of treatment for the adult population, further information can be found in section
5a.ii.
9
The authority of scientific expertise responsible for evaluating the safety and efficacy of medicinal products.
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3b. Regulatory Authorities
Regulatory Authorities, sometimes referred to as agencies or competent authorities, are the bodies
of scientific expertise responsible for the evaluation of medicinal products. They typically hold the
legal mandate to protect public health and are required to ensure that medicines are safe and
effective but also to promote effective innovation and development of new medicinal products.
Within the EU and around the world working practices and in some cases terminologies differ but
the principle behind their activities is consistent.
3b.i. The European Medicines Agency (EMA)
Creation of the EMA and Legal Basis
The European Agency for the Evaluation of Medicinal Products was set up in 1995 with funding from
the European Union and the Pharmaceutical Industry. It was later renamed as the European
Medicines Agency in 2004. The intent was to harmonize, but not replace the work of the National
Competent Agencies (NCAs) (3b.ii). Industry stood to gain on the basis that it would help reduce the
cost of applying for licence in each individual member state and remove the potential for
protectionist refusal of new medicines which may compete with those already produced by
domestic drug companies.
The legal basis for the EMA is laid out in Regulation (EC) 726/2004 (4). The EMA is responsible for the
protection and promotion of human and animal health, through the evaluation and supervision of
medicines for human and veterinary use. The EMA achieves this by coordinating the existing
scientific resources placed at its disposal by Member States. The EMA does not hold the legal
authority for the authorisation, suspension or revocation of medicinal products and can only provide
a recommendation based on its expert opinion. The European Commission is responsible for the
adoption of the necessary provisional measures following consideration of the opinion.
Operation of the EMA
The European Medicines Agency is the decentralised regulatory agency of the EU and coordinator of
most collaborative regulatory activities across Europe. The most obvious activity of the EMA is its
role in the centralised procedure10 (CP) where it coordinates the competent review of a product to
grant and maintain a “community licence” valid throughout the European Union (EU) and EEA-EFTA
states11 (2c). The EMA can be considered the ‘hub’ of the European regulatory network and is
therefore a key player in driving the development of regulatory science in the EU.
The EMA works with a network of over 4,500 ‘European experts’ who serve as members of the
committees, working parties and assessment teams which form the basis of available scientific
expertise. The scientific expertise available to the EMA is organised into committees in which
10
The centralised procedure provides the facility for an applicant to apply for a single MA valid in all Member
States of the EU.
11
Iceland, Liechtenstein and Norway.
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scientific expertise of all member states, EU and EEA-EFTA, are represented. Some of the
committees also include representatives of patient and health care professional (HCP) organisations.
Committee for Medicinal Products for Human Use (CHMP)
The CHMP is the committee responsible for the competent evaluation and supervision of medicinal
products authorised through the centralised procedure. In the Decentralised and Mutual
Recognition procedure (2c) the CHMP arbitrates in cases of disagreement between member states.
The CHMP plays an important role in EU-wide PhV activity, closely monitoring potential safety
concerns and where necessary making recommendations to the European Commission regarding
changes to a medicines MA, or its suspension/withdrawal from the market. The CHMP is also
responsible for the provision of scientific advice and preparation scientific and regulatory guidelines
for the pharmaceutical industry. The EMA has published on its website the rules governing the
operation of CHMP as well as the CHMP work plan which sets out the priority objectives linked to
the EMAs development (5a). (5) (6)
Other Committees
CVMP – Committee for Medicinal Products for Veterinary Use: equivalent of CHMP relevant to
veterinary products
COMP – Committee for Orphan Medicinal Products: responsible for reviewing applications for
‘orphan medicinal product designation’12.
HMPC – Committee on Herbal Medicinal Products
PDCO – Paediatric Committee: Responsible for agreeing the Paediatric Investigation Plan (PIP)13
CAT – Committee for Advanced Therapy Medicinal Products: Prepares a draft opinion on Advanced
Therapy Medicinal Product applications prior to CHMP opinion.
PRAC – Pharmacovigilance Risk Assessment Committee: responsible for monitoring and assessing
safety issues for human medicines. Its opinions are considered by the CHMP in adopting opinions.
Other Activities of the EMA
The EMA is responsible for the implementation of a set of pan-European systems and databases
such as EudraVigilance (5a.i), EudraCT14 and EudraPharm15. (7)
12
Orphan Designation is an incentive provided to products which are developed to treat rare diseases and
would therefore be likely non-profitable. It provides for additional 10 years market exclusivity, preventing the
authorisation of competing products using a similar substance unless it can prove exemption criteria described
in the Orphan Drugs legislation; Reg (EC) 141/2000, for example Clinical Superiority.
13
Paediatric Investigation Plans are a requirement for all innovative medicinal products in the EU. They set out
how a sponsor will research the use of the product in children, providing data to support prescribing guidance.
See 5a.ii for further information.
14
Database of Clinical Trials conducted within the EU
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3b.ii National Competent Agencies (NCAs)
Typically each country has its own regulatory agency responsible for the review and surveillance of
medicinal products. In each country the remit of the NCA is individual and working practices can vary
significantly. The decision on pricing and reimbursement16 remains a purely national issue and is
increasingly undertaken with the aid of assessments from Health Technology Assessment (HTA)
agencies which are sometimes incorporated into the NCA. HTA assessments typically involve a
comparative assessment of therapeutic benefit against current standard of care.
Heads of Medicines Agencies (HMA)
Established in 1995, the HMA is a network of the Heads of NCAs whose organisations are responsible
for the regulation of medicinal products for human and veterinary use in the European Economic
Area. It focuses on collaboration and harmonisation of national agencies and the smooth functioning
of decentralised and mutual recognition procedures (3c). The HMA works in close collaboration with
EMA and this framework is integral to the smooth functioning of the European Regulatory Network.
(8)
3b.iii Non-EU Regulatory Authorities
Outside the EU medicines are typically regulated on a purely national basis although increasingly
work sharing networks are being developed in Asia and Latin America. Each country has its own
requirements and regulations providing a highly dynamic environment. Policies in the Emerging
Markets17 are often influenced by political and economic drivers as well as healthcare provision. An
example of this would be the requirement of China to conduct clinical trials in Chinese patients and
therefore force an investment in the country. This is justified on ethical factors. Regulatory agencies
in the emerging markets are developing quickly to meet the increasing demands being placed upon
them. In many instances these countries will reference the decisions of the US FDA or EMA for the
review of medicines, or adopt practices and legal frameworks already seen in these more developed
environments.
15
Database of Medicinal Products authorised through the centralised procedure. Provides public access to
SmPC and PiL.
16
Typically a medicine has a negotiated price for which the company sells the product and a negotiated
reimbursement value, the amount which the payor (typically the state in Europe) will cover these costs.
17
Emerging Markets in the field of medicine regulation typically refers to all countries other than the USA, EU,
Japan, Australia-New Zealand and Canada.
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US Food and Drug Administration (FDA)
The FDA is an agency within the department of Health and Human Services and has the
responsibility for protecting public health. In addition to regulating the use of medicinal products for
people and animals the FDA is responsible for regulating food and tobacco products. Unlike the EMA
the FDA is a centralised agency which reports directly to the national government. (9) On the global
stage the FDA is a key player in the International Conference on Harmonisation (ICH) along with EMA
and the Japanese Health Authority. ICH provides a platform for the global harmonisation of
regulatory requirements and to date more than 40 harmonised guidelines have been developed on
technical matters in the areas of quality, efficacy and safety. (10)
World Health Organisation (WHO)
The WHO plays a significant role in the global regulation of medicines producing many guidelines
that are widely adopted. Perhaps the foremost of these are the guidelines on Good Manufacturing
Practice (GMP) and Good Clinical Practice (GCP) which set out formalised standards that all
medicinal products must adhere too. These are very similar to the guidelines present in the EU and
USA which have been tempered slightly to fit with regional legislation.
3c Regulatory Procedures in the EU
The Centralised Procedure (CP)
The CP, introduced in 1995, is governed by Regulation (EU) 2001/83 and provides a MA valid
throughout the EU. The CP is mandatory for new products derived from biotechnology processes18
and Orphan drugs. It is also mandatory for products containing an active substance (not authorised
in the EU before May 2004) which are intended for the treatment of AIDs, cancer,
neurodegenerative disorders, auto-immune diseases, viral diseases and diabetes. For other products
the procedure is optional provided it represents an innovation or its authorisation would be in the
interest of public or animal health. In practice the majority of new chemical entities (NCEs) are
authorised via the CP.
Products authorised through the centralised procedure are evaluated by a rapporteur and corapporteur, members of the CHMP representing Member States (MS), who hold specific expertise in
the relevant therapeutic area. Their analysis and decisions are peer-reviewed through the CHMP
which provide an eventual opinion on authorisation by majority vote.
18
This includes genetically engineered products (often referred to as biologicals) where the active ingredient is
grown in a cell culture, and advanced therapy products including gene therapy, somatic cell therapy or tissue
engineered medicines.
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Outline of the CHMP (CP) Approval Process
Figure 5: Timeline for Centralised Procedure submission
Built into the procedure are several points of interaction between the sponsor company and the
CHMP. Most significant of these are at Day 120 and 180. The clock stop following the Day 120 List of
Questions typically lasts 3 months. It is for this reason that Pfizer anticipate a total length of a 15
month procedure. At the end of the procedure the CHMP will adopt a positive or negative opinion as
to whether the product should receive a MA.
The CHMP opinion is provided to the European Commission who must take the decision on whether
or not to licence the product. The Commission usually follows the opinion of the CHMP however
there are exceptions. One such example is included; Annex II. Once a community MA has been
granted it is valid for 5 years, once this has elapsed it is reviewed indefinitely.
The benefits of using the CP are that a single EU license is gained which covers all MS. This not only
simplifies the procedure of applying for a licence but reduces the burden of maintaining the product
as the MAH only has to interact with one regulatory agency and only provide updates to a single
Summary of Product Characteristics (SmPC)19 and Patient Information Leaflet (PIL)20. One
disadvantage to the procedure is that the sponsor cannot choose the CHMP members assigned as
rapporteurs (which is possible in MRP/DCP). This procedure may not be appropriate for products
which are only going to be marketed in a single or low number of MS.
19
A document designed to provide information to Health Care Professionals (HCPs). It is also the foundation
for a products marketing programme.
20
The package insert provided to patients giving details of the medicine and instructions for use.
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Mutual Recognition Procedure (MRP)
The MRP procedure provides a framework to allow MS to reference the Marketing Authorisation
decision of another MS. In this pathway the sponsor company chooses the MS in which to file for a
national MA, known as the Reference Member State or RMA. The other countries in which the
sponsor would like to licence the drug are requested to recognise this approval if successful and are
termed the Concerned Member States (CMS). The RMS performs the initial product review and if
successful grants the first regulatory approval. This will be the first country in which the product can
be marketed. The CMS are then asked to mutually recognise the assessment report and SmPC
provided by the RMS within 90 days.
The benefits of the MRP procedure are that the applicant has control over choosing the RMS and
CMS. This can allow a sponsor to focus its resources on a few key markets. Also potentially beneficial
where a product will be co-marketed with another company the MRP facilitates multiple trade
names. The biggest downside to the procedure is that CMS often disagree with the assessment
report produced by the RMS and this can hold up the procedure and cause delays. This is
exasperated by countries with more developed regulatory agencies tending to conduct their own
detailed reviews; and has the effect of duplicating work. The MRP provides a separate MA in each
country, each with its own SmPC. This can represent a resource burden for the Marketing
Authorisation Holder (MAH) to manage the additional interactions and requirements this creates.
Decentralised Procedure (DP/DCP)
Introduced in 2005 the DP is an evolution of the MRP. The intention was to reduce the occurrence
and impact of disputes between MS which cause delays to authorisation. The DP is similar to the
MRP however timelines are shorter (maximum of 210 days, split into two assessment phases, with
opportunities to close out procedure ahead of time if consensus is reached between RMS, CMS and
applicant) and the MAA is submitted simultaneously to the RMS and CMS. The RMS prepares a draft
assessment report which is shared with all the CMS for reflection and judgement. The rationale
being that by providing CMS early input into the evaluation any potential concerns can be addressed
in a timely manner. If approved the applicant receives the same MA in all chosen MS at the same
time.
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Figure 6: Diagram of DP review pathway
Decentralized Procedure
Application
in RMS+
CMSs
Consultation RMS,
CMSs, applicant
Day 1
National MAs
2
30 days
National MAs
3
2
14 days
105 days
Consensus
30 days
Clock stop?
Max 3 months
3
Consensus
1
No consensus
No consensus
National MAs
Day 150
2
30 days
30 days
Day 120
Consensus
National MAs
Day 210
3
Break-out
2
30 days
3
max 30 days
25 days
5 days
Consensus
No consensus
CMD process
Step I
Step II
Day 180: RMS +
appl. clarification
No consensus
20
CMD = Coordination Group for Mutual Recognition and Decentralised Procedures. If after CMD opinion there is no
agreement it goes to arbitration.
The procedure can be used for any products which are not authorised within the community and are
not mandatory for the CP pathway. It is often favoured by less complex applications such as
generics21.
National Procedures
National procedures are rarely used for the filing of prescription medicines which are generally
developed by large multinational corporations. Pfizer however still maintains a significant number of
nationally approved licenses for older products which were authorised before the implementation of
the procedures described above. National licences are now used more frequently by small and
medium-sized enterprises producing generic or consumer health products. In these procedures the
applicant applies directly to the NCA and follows national review procedures which vary significantly
from country to country.
21
Copy Drugs which have to show they are “essentially similar” a product currently on the market. They
therefore only have to provide comparative quality data. There is no requirement for full non-clinical and
clinical data for generic drugs. Bioequivalence studies are usually sufficient.
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Clinical Trial Applications (CTAs)
To conduct a clinical study in any state it must first be approved by national procedures in
accordance with the clinical trial directive (2001/20 EC). The approval of CTAs is within member state
competence. The decision is split into a scientific approval by the competent authority and an ethical
approval for which the assessment is typically made by ethics committees.
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Worldwide Safety and Regulatory at Pfizer
Worldwide Safety and Regulatory (WSR) is the business line responsible for interactions between
Pfizer and Regulatory Authorities.
4a. Organisational Structure
WSR is a functional line of Worldwide Research and Development (WRD).
Figure 7: Functional lines within WRD.
WSR has within it Worldwide Regulatory Strategy (WRS), Worldwide Safety Strategy (WSS) and
Worldwide Safety and Regulatory Operations (WSRO).
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4b. Department Roles and Responsibilities (Worldwide Regulatory Strategy (WRS))
Mission Statement
WRS delivers excellence through trusted compliant and innovative strategies so patients, consumers
and Pfizer will benefit from our valued products.
Figure 8: Poster documenting WRS roles and Activities, produced for Internal Sandwich Site Event
The primary function of WRS is developing strategies to bring products to market and maintain their
authorisation through the quickest, most feasible route. In the discovery and pre-clinical and clinical
phase WRS helps identify potential regulatory risks, create mitigation plans and manage
relationships with regulatory authorities. Additionally in the clinical development phase (I – III) WRS
colleagues open and maintain Clinical trial applications (CTAs) and Investigational new drug
applications (INDs)22. In the registration phase WRS are the focal point for external contact and coordinate response actions to regulatory agency requests and questions. WRS also drives the label
(SmPC) development, both internally and through negotiations with regulators, which is
fundamental to the successful marketing of the product. Post authorisation WRS is responsible for
coordinating the maintenance of authorisation; renewing products, providing updates to
information and responding to safety signals etc.
Worldwide Regulatory Strategy (WRS) is responsible for managing the company’s relationship with
regulatory agencies. All communications and submissions made to regulators are checked and
22
US equivalent of a Clinical Trial Application
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signed by WRS. It is important to realise that this activity applies to all Pfizer products, in all
countries at every stage in the product lifecycle. This role is also adopted at the above product level
where WRS represents Pfizer in Policy level discussions, providing input and influence to future
practices and requirements applicable to the regulation of medicinal products. Effectively managing
these relationships to ensure that all information provided is accurate and advocacy positions
adopted are reasoned is critical to Pfizers reputation.
Role of a Global Regulatory Lead (GRL)
The majority of the WRS EU group is made up of product strategists and Regulatory Leads. A Global
Regulatory Lead (GRL)23 is accountable for regulatory strategy. The RL is the “go to” person on the
project team. The regulatory lead is responsible for communication and alignment within the
regulatory sub-team. The RL is responsible for internal communication and reporting. By strategy it
means plans and timelines including balancing risk vs time and working out the most appropriate
(incorporates speed and cost) way of overcoming regulatory hurdles to getting and maintaining a
product on the market.
Figure 9: Interactions of the GRL with Regulatory colleagues and the product’s core team.
What does a GRL Do?
 Provides advice on regulations and the implications to the core team.
 Defines and documents the regulatory strategy.
 Helps to develop the product label.
 Manages the regulatory risk log.
 Manage regulatory agency meetings and interactions.
 IND/CTA preparation.
 Optimize a marketable label (SmPC in Europe)
Regulatory do not prepare applications to regulatory authorities, this is done by the submissions
group. However, WRS plays a leading role in defining the content of the applications.
23
GRLs are sometimes termed GRPLs - Global regulatory product leads however this acronym is also used for
Global regulatory portfolio lead within Pfizer. Portfolio leads operate at an above product level on a group of
products within the same therapeutic area.
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Regulatory Policy
The Regulatory Policy function monitors changes in the external environment, assesses the business
implications and develops advocacy plans to influence the environment in a way favourable to
Pfizer.
5a. Regulatory and Policy Environment 2011-2012
Regulator – Industry Interaction
Presently regulator interaction, particularly with EMA, is more restricted to formal format than
previously seen. Political pressure, fallout from the mediator scandal24 and the embarrassment
caused by the consultancy role adopted by EMA’s previous executive director immediately after
breaking affiliation with the agency are the principal reasons. Therefore most policy-related
interactions with EMA have to occur through trade associations. On a product specific level, it is in
some cases still possible for the sponsor to contact the rapporteur directly (3c) however any
documentation must be shared through the formal process via the Project Team Leader (PTL)25. On
the global scale ICH is another example where Industry involvement has been reduced as a result of
political pressure from the EU which threatened to withdraw from the agreement if Industry
continued to have any influence in the later decision stages.
Transparency
There is a drive within the EMA for increased transparency throughout the regulatory process. In
recent years the European Public Assessment Report (EPAR)26 has been revised to more clearly
present the reasons for CHMP opinion in the Benefit/Risk Decision. This has been highlighted as an
area of ongoing work in the EMA roadmap to 2015 (11). Sponsors can no longer expect to benefit
from sweeping confidentiality of product information as facilities such as freedom of information
requests and the EMAs policy of providing as much information as possible in accordance with EU
law mean a MAH will have to justify the omission of information piece by piece from any given
document. Furthermore the EMA plans to begin publishing much more information on medicinal
products upon its website as soon as it has the IT infrastructure required.
The EMA has also responded to calls to tighten up its conflict of interest requirements however in
the view of the European Parliament these efforts are not sufficient and the EMA needs to take
further action. This was the reason cited for postponing signing off the EMA budget for 2011 in May
which remains uncertain (12). Further information can be found in the EMA’s transparency Policy
(13).
24
Mediator, a product of Servier (French company) has been identified as the cause of a significant number of
fatalities. It was kept on the market in France for several years after withdrawal from most European markets
following safety concerns.
25
Project team leader is the primary contact at the EMA who coordinates the exchange of information
between applicant and scientific experts.
26
A publically available document which summarises the scientific assessment of medicinal products.
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Stimulating Innovation and Innovative Medicines Initiative (IMI)
It is within the remit of the EC and EMA to stimulate innovation for the benefit of public health.
There are many initiatives which look to facilitate the development of medicines which would
otherwise be non-economically attractive, for example orphan designation (3b.i). Through the EC DG
Innovation and research the Framework Programme for Research provides funding for underresearched areas such as antimicrobial resistance and supports SMEs. Pharmaceuticals sector will
receive the 3rd greatest sum under FP7 (2013) (14).
The Innovative Medicines Initiative (IMI) is a public-private partnership between the European
Commission and EFPIA (representing the pharmaceutical Industry). Its aim is to address some of the
blockages in the development of new medicines. IMI has many projects which are currently mostly
focused upon research issues. The projects are long term however the impacts are expected to be
significant. It is important that the scientific decisions resulting from IMI are accepted as valid for use
in regulatory decisions. The focus of IMI is gradually shifting towards more regulatory focused
projects, shown for example by the inclusion of “incorporating real life clinical data in drug
development” in the 7th call for proposals (15). This trend will likely continue in IMI 2 due to Industry
interest if it becomes a reality.
Non-Regulatory Specific Items
Patient Access to Medicines
The greatest challenge facing European health care systems is sustainability. With tension applied on
state purse strings healthcare, and medicine, budgets are being cut. With an ageing population
which is better cared for the prevalence of chronic disease is increasing and the current model
struggling to fund it. An ever increasing proportion of medicines being authorised are failing to
achieve reimbursement and as a result access is denied to the majority of patients. At present the
signs suggest that this phenomenon will be exaggerated in the future.
Falsified Medicines
There has been an increasing movement seeking to protect the community from the detrimental
health effects associated with fake medicine. In June 2011 the EU amending directive 2001/83 on
falsified medicines entering the legal supply chain was released (14). The directive made certain
provisions designed to protect the public from exposure to falsified medicines. Member states have
until January 2013 to begin applying the measures in national law. The topic has also been a
controversial area on the policy front with EFPIA and partnering associations proposing the
European Stakeholder Model (ESM) (15) which has been criticised in some quarters for having
implications serving to protect market exclusivity for innovative products.
Drug Shortages
The drug shortages crisis seen in 2011 and 2012 has been largely confined to the USA however the
ripple effect has been felt in Europe. Policy makers and regulators are now starting to look at the
reliability of licensed manufacturing facilities as documented. To date the issue has focused on
generic manufacturers listing several manufacturing sites for a product but in reality only
manufacturing out of one, whilst the others are in a manufacture-ready state for the specific
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product. The spotlight has not yet focused on the innovative industry where similar issues may exist
in some capacity.
Further information is available in the EUCANZ Regulatory Policy Environment Scan in Annex . A
summary of key policy topics can be found in 5d.
5b. Legislation and Guidances in the EU
The documents which detail requirements to be met by stakeholders in the provision of medicinal
products to patients can be broadly split into legislation and guidance, sometimes termed soft law.
Legislation
On a pan-EU scale legislation is born from the European Commission (EC) and split into Directives
and Regulations. Directives are binding in requiring MS to achieve a certain result without dictating
the means of achieving that result. This affords MS some leeway as to the exact rules to be adopted.
Regulations are self-executing and do not require any implementing measures. The legal basis for
Directives and Regulations is set out in Article 288 of the Treaty on the Functioning of the European
Union:
Article 288
To exercise the Union's competences, the institutions shall adopt regulations, directives, decisions,
recommendations and opinions.
A regulation shall have general application. It shall be binding in its entirety and directly applicable in
all Member States.
A directive shall be binding, as to the result to be achieved, upon each Member State to which it is
addressed, but shall leave to the national authorities the choice of form and methods.
A decision shall be binding in its entirety upon those to whom it is addressed.
Recommendations and opinions shall have no binding force.
The implications to the Pharmaceutical Industry of implementing requirements as directives are that
national authorities can introduce non-harmonious requirements which can be an additional burden
to Industry. Regulations enforce more harmonious implementation of the text; however issues can
arise if the legislation proves to be unwieldy and non efficient as there is less room to deviate from
the exact text.
The legislative procedure in the EU is typically a slow process taking several years for new legislation
or amendments to be adopted. The co-decision procedure used requires that the Council and the
European Parliament (EP) both agree and approve the text, first drafted by the EC. The procedure is
designed to ensure a balance of the 3 powers, the commission, council and EP. These represent the
interests of the union, member states and democratic interests respectively.
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Figure 10: The Co-Decision procedure for the enforcement of legislation in the EU.
Pharmaceuticals comes within the remit of Commissioner Dalli, DG SANCO27 at the commission. DG
SANCO is therefore responsible for the first draft of any legislation referring directly to the Pharma
Industry. This will be reviewed by other interested DGs at the commission, for example Enterprise
and Industry. Any texts must be agreed by all Commissioners prior to release into the co-decision
procedure.
27
Directorate General for Health and Consumers
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Guidances
Underpinning the legislation there are many guidelines pertaining to medicinal products for
pharmaceutical manufacturers to follow. These guidelines hold no legal force and are usually
produced with the intent of assisting Industry in meeting the obligations set out by legislation.
Guidance can be broadly split into two categories, regulatory and scientific. Regulatory guidelines
typically come from the EC and/or EMA and set out procedures. These provide industry with
instruction on how to submit certain applications (e.g. renewals) and what can be expected from
involved parties through the procedure. Scientific Guidelines are intended to provide a basis for
practical harmonisation of the manner in which the EU Member States and the EMA interpret and
apply the detailed requirements for the demonstration of quality, safety and efficacy contained in
the Community Directives. They also help to ensure that applications for marketing authorisation are
prepared in a manner that will be recognized as valid by the EMA.
5c. Trade Associations and Policy Interactions
Trade Associations
Funded by their member companies trade associations provide a means for collaboration between
members and a basis for lobbying as a unified voice for the Industry they represent. The two most
significant trade associations serving large scale innovative pharmaceutical companies28 are PhRMA
in the USA and EFPIA in Europe.
EFPIA
The European Federation of Pharmaceutical
Industries and Associations, EFPIA, is the
principal trade association acting on behalf of
pharmaceuticals Industry in the EU. Within
EFPIA there are two member associations,
EVM and EBE. These are the European Vaccine
Manufacturers and European Biological Enterprises respectively and represent the interests of
manufacturers of these subgroups of medicinal products. EFPIA has been a key driver in many
initiatives in the EU. Perhaps the best known of these is the Innovative Medicines Initiative (IMI), a
public-private partnership and joint undertaking of the EC and EFPIA. IMI aims to speed the
development of better and safer medicines for patients (5a). Another area of great activity recently
has been the controversial European Stakeholder Model proposal from EFPIA, in collaboration with
wholesaler and pharmacy associations, to combat falsified and counterfeit medicines. (11)
The segment of EFPIA devoted to regulatory affairs is split into several committees:
 Scientific, Regulatory & Manufacturing Policy Committee (SRMPC) – this is the main policy
governance committee that determines overarching policy objectives at a high level.
28
Innovative pharmaceutical companies are those which research and develop their own medicines as
opposed to generic manufacturers which reproduce previously authorised medicines once they lose patent
protection.
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


European Regulatory Liaison Committee (ERLC) – responsible for the production of more
detailed policy positions in the regulatory field
Clinical Development Committee (CDC) – oversees policy activities pertaining to clinical
development.
Temporary Working Groups (TWG) – these are established on a temporary basis to focus on
specific issues where a high level of policy activity is required in the short term. They report
directly into SRMPC.
Other Trade Associations
At an EU level there are some other trade associations which have an advocacy role. Some of the
more notable are:
 Europabio – represents the biotechnology Industry, Pfizer is a member
 EGA – European Generics Association represents the non-innovative pharmaceutical
Industry
 EUCOPE – represents mid-sized innovative pharmaceutical companies
There are also many trade associations at a national level which may influence policy, predominantly
focusing on the MS however scope of activity can have an influence on Pan-EU policy. In the UK the
Association of British Pharmaceuticals Industries (ABPI) is an example of a national trade association
active on European level, largely due to policy activity of MHRA (UK NCA).
Policy Interactions
A significant amount of interaction with regulators and legislators is achieved through the trade
associations. Typically it is trade association representatives that are invited to stakeholder meetings
and through trade associations that Industry is invited to comment on closed consultations29. Trade
associations also provide the principle fora for interactions within Industry. These most commonly
involve the drafting and agreement of positions and provision of data to support them.
There are also other platforms for policy discussions which provide the opportunity to influence
regulators and Industry peers. Examples of these are DIA30 and TOPRA31 meetings. It is also in some
cases possible to establish meetings directly with commission staff and Members of European
Parliament as relevant on specific topics. It is very challenging for a company to engage directly with
regulators on policy issues due to concerns of conflicts of interests (5a).
29
Many draft legal and guideline texts are put out for consultation prior to finalisation. These consultations are
often public (particularly legal texts) however in some cases, for example where technical expertise is required,
the consultation is closed. This is in effect an invitational consultation.
30
Drug Information Association – A non-profit organisation funded by its members supporting knowledge
exchange an collaboration in Pharmaceuticals sector.
31
The Organisation for Professionals in Regulatory Affairs – member organisation focusing on sharing
knowledge, ideas and education in Regulatory Affairs. Membership includes regulators, Industry professionals
and freelancers.
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5d. Regulatory Policy at Pfizer
The Regulatory Policy function within Pfizer has a regionally focused structure, with EU Regulatory
Policy reporting through the WRS-International organisation. EU Regulatory Policy has a small core
team which coordinates policy activity, some of the workload is shared with other WRS colleagues.
Figure 11: Activity of EU Regulatory Policy
The Regulatory Policy function monitors changes in the external environment, assesses the business
implications and develops advocacy plans to influence the environment in a way favourable to
Pfizer.
Changes in the environment can be very varied in nature. Some examples include new legislation or
guidelines, the result of political pressure and reactions to crisis examples. The causation for
environmental changes can be complex and the underlying reasons must be carefully considered in
the development of policy positions.
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Organisational Structure and Internal Interactions
Figure 12: EU Regulatory Policy Team and Reporting Structure
Regional Policy Team in Europe
WRS-I Head
(J. Thompson)
Nick Sykes
Ed Cooper
(Industrial Trainee)
Sharon Gorman
-1-
EU Regulatory Policy Reports through the WRS International line.
There is a strong collaboration between Regulatory Policy and Government Affairs/worldwide policy.
This is crucial as many of the topics overlap these fields and it is important that activities are
coordinated to prevent duplication of effort and ensure Pfizer is acting with “one voice”.
Regulatory Policy partners very closely with the regulatory function of the Business Units. This
interaction helps bring the commercial relevance to the proposed changes and Pfizer positions by
analysing the effect it will have on the portfolio. Regulatory Policy also maintains a close relationship
with Regulatory CMC (Chemistry, Manufacturing and Controls) for counsel on issues pertaining to
manufacturing.
Mechanisms of Internal Stakeholder Consultation and Policy Governance
In the development of Policy Positions there are 3 typical stages of consultation.
 Policy Forum: Uses expertise from WRS to contribute to the policy agenda and hold in depth
discussions on the formation of policy positions.
 Standing Committee: A cross-functional team which helps develop policy positions, provides
a first level of endorsement and supports Pfizers relationship with Regulators.
 CMEI – Clinical Medical Excellence and Innovation board, provides a higher level of
endorsement for positions where required.
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Figure 13: EU Regulatory Policy Governance
Priority Policy Topics
To focus advocacy activities on key areas of high importance Priority Policy Topics are identified and
reviewed on a regular basis. These are selected based upon their impact to the Pfizer business and
potential to have a positive impact. The current priority topics (July 2012) are summarised below, for
more details see EUCANZ Regulatory Environment Scan in Annex II.

Market Access / HTA: The benefit/risk regulatory assessment and the health technology
comparative effectiveness assessments overlap. This area of policy focuses on how the
sector needs to develop to allow pharmaceutical companies to most efficiently meet the
needs of both these assessments.

EU Clinical Trials Environment: The last ten to fifteen years has seen a marked decline in the
number of clinical trials undertaken in the EU. There are several factors making the EU a less
attractive region in which to conduct clinical trials including legislative bureaucracy. The aim
is to increase the feasibility of conducting more clinical trials in the EU and ensuring that it
provides for innovative trial paradigms that may be used in the future.

EMA Evolution: The EMA is continuously looking to develop and improve the way it
operates. The focus here is to ensure it does so in collaboration with Industry to enhance the
provision of safe and effective medicines and not create unnecessary hurdles.

Pharmacovigilance Legislation: The new PhV legislation provides regulators with the tools to
more effectively reassess products post authorisation. This places new obligations on
companies and regulators to monitor safety signals. There is also an opportunity to utilise
these tools to speed patient access to medicines by collecting a greater proportion of data
post authorisation. One initiative to utilise this is adaptive licensing. Insert Reference Here
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o
E-submission of medicinal product information (A57(2) database): A new
requirement for Industry to submit and maintain the details of every license held
within the EU to the EVMPD32. The focus of advocacy work is to ensure that EMA
works with Industry to achieve this goal in a pragmatic way and uses the new
facilties provided efficiently to reduce duplication of effort.

Biosimilars: Biosimilars are biological products which are developed as a copy of an already
licensed reference product. In this comparatively juvenile area of regulatory science which is
fast evolving advocacy work focuses on correctly presenting the science and encouraging
biosimilar use whilst ensuring patient safety is maintained.

Paediatrics: Historically medicines have been poorly studied for use in children due to the
poor economic return. Legislation in the EU has forced companies to study paediatric use
where appropriate. The legislation and its implementation has however caused many
bottlenecks of bureaucracy and been very difficult to manage. Work here focuses on
effecting the necessary changes to reduce unnecessary burden upon industry.

Personalised Medicine: With Pfizer’s approach to medicine development shifting towards
precision medicine for specific patients it is important that the environment is prepared to
accept the new paradigm of drug discovery and provision. Advocacy efforts are focused on
increasing the understanding that legislation adopted today must provide for the medicines
of tomorrow.

Labelling in 21st century: The EC, regulators and Industry agree that the information
provided to patients needs to be improved. Combined with this is a review of the SmPC
provided to HCPs and pharmacists. Electronic provision of information is being considered.
The aim is to provide up-to date information quickly and to allow more flexibility in
presentation to improve patient understanding.

Transparency: A topic of high focus with considerable political pressure. Regulatory
documents provided by MAHs are more frequently becoming publically accessible and public
assessment reports are much more detailed. It is important here to protect confidential
information and encourage regulatory agencies to adopt the same transparency principles
as forced upon companies.

Benefit / Risk Decision-Making and Communication: The methodology of the Benefit Risk
decision is currently receiving extensive consideration. There are initiatives looking at adding
a quantitative element to the decision (ProACT-URL)33 and at allowing earlier access to
32
Eudravigilance Medicinal Product Dictionary – A database of all medicinal products and a PhV tool which is
under development by EMA and Industry.
33
A quantitative B/R Decision process developed by CHMP. ProACT-URL stands for Problems, Objectives,
Alternatives, Consequences, Trade-offs – Uncertainty, Risk-tolerance, Linked Decisions.
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medicines through continuous assessment (Adaptive Licensing)34. EMA are also interested in
the possibilities of involving physicians and patients in the process. The EMA has already
made changes to the European public Assessment Report (EPAR) and is looking at further
improving the communication of decisions. This is an area of significant interest to Pfizer
who are involved in Adaptive licensing and supportive of programmes aiming to enhance the
benefit / risk decision.
34
Adaptive Licensing is a project being run by NEWDIGS (a group at MIT) which has received some support
from CHMP, most notably Hans Georg Eichler. It looks to initially authorise a product based on a small
population most likely to benefit from the product. This can then be expanded as more data is generated.
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Personal Activities and Responsibilities
6a. Key Topic Areas
Within the EU regulatory policy team activities were coordinated by splitting priority policy topics up
and assigning them each a lead who was the main point of contact on the issue. Due to the
maternity leave of a colleague my assigned responsibilities were juggled in the course of the year.
6a.i Article 57 (2) of Pharmacovigilance Regulation 726/2004 (EC)
Introduction
Article 57 of Regulation (EC) No 726/200435 as amended by Regulation (EU) 1235/2010 and Directive
2010/84/EU (pharmacovigilance legislation) requires that a publically available database of all
medicinal products authorised within the community is available by July 2nd 2012. Therefore MAHs
are required to submit the relevant information on all medicinal products authorised or registered
within the EU using the format outlined by the EMA. The Eudravigilance Medicinal Product
Dictionary (EVMPD) is the database that will be used for this purpose. This presented Industry with a
huge challenge in locating, preparing and submitting the information for all products. In the instance
of Pfizer this represented thousands of licences.
Background
The creation of this requirement in legislation stems from an appreciation that it is unacceptable for
European Authorities not to have a complete list of products available upon the market within the
EU. It was realised that in the event that a safety signal was realised with an active ingredient or
other chemical within a product appropriate actions could be taken for that product but not for
other products including the same ingredient. As a result the EU would need a complete database of
all available products, their active product and excipients to protect the public in the instance of a
pharmacovigilance signal. The database would be further used to asses adverse event reports known
as Individual Case Study Reports (ICSRs).
Initial Requirements
In the initial legal notice and ‘detailed guidance on submission of information on medicinal products
for human use by marketing authorisation holders’ of July 1st 2011, the EMA required a huge amount
of data, some of which went beyond the details included in a MAA. The short timeframe and huge
scale of the work required to complete this task made it quite untenable and resulting in extensive
lobbying from the Pharmaceutical Industry. As a result the scope of the requirements were reduced
to only those essential to meet the obligation set out in the legal text and of direct benefit to public
health, however the date of implementation could not be altered.
Reduced Scope Requirements
For every individual medicinal product licence held in the EU the following had to be submitted to
the EMA by July 2nd 2012.
 Name of Product
35
Regulation of the European Parliament and of the Council; laying down Community procedures for the
authorisation and supervision of medicinal products for human and veterinary use and establishing a European
Medicines Agency.
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
Name, address and contact details for the qualified person responsible for
pharmacovigilance (non-mandatory)
 Location of the pharmacovigilance master file
 Therapeutic indication
 Description of the active substances, excipients and adjuvants
 Description of a medical device as part of the authorised product
 Description of the package (pack size)
 Submission of approved SmPC in the local language for each authorised product
 Designation of additional monitoring for products.
An updated legal notice detailing the reduced scope was published in March 2012.
In reality Industry was unable to comply completely with the deadline however huge efforts and
resources were placed in aid of this project.
Maintenance of EVMPD
Once uploaded the product information in the dictionary will have to be kept up to date and reflect
changes that occur to the licence of the product. This will be achieved through Industry submitting
update messages making the relevant changes. At present the detailed requirements for Industry
are not known with only a few concepts so far agreed with EMA. There will be a full day stakeholder
meeting on September 12th where EMA and Industry will present proposals. Following this detailed
guidance for Industry will be released by the EMA.
The details of maintenance requirements are of significant importance to Pfizer as the required
timelines and the inclusion or otherwise of information fields and documents as mandatory for
updates may force internal process modification. In the long term Pfizer will look to automate the
process to the greatest degree possible.
Roadmap of EVMPD
The legislation requires that the migration of EVMPD to ISO IDMP36 standards is implemented by July
2nd 2016. These standards, once finalised, will determine the product information to be held in the
EVMPD by legal requirement. The IDMP standards are being worked through the ICH process and
could be finalised by the end of 2012. The EMA envisages the EVMPD becoming the ‘backbone of the
European Regulatory Network’ (Noel Wathion, EMA) and whilst the regulatory agency’s full
ambitions are unknown it is clear that they see it as an opportunity for development. The expansion
of the database to additional data fields and submission requirements for newly mandatory
information is yet to be detailed and agreed with Industry.
Policy Arguments
All policy positions advocated by Pfizer were worked up through EFPIA, due to the closed nature of
the consultations Pfizer has not produced any individual policy positions.
Prior to the reduction in scope EFPIA’s lobbying focused on the unachievable nature of the
requirement. The removal of several data fields and selection as some additional as not mandatory
in February 2012 was a great success which brought the task into a reasonable proportion. Since the
agreement at the stakeholder meeting in February the focus has been on maintenance activities and
data clean up. Industry’s positions are seeking for efficient and pragmatic implementation of
processes that provide accurate information to patients in a timely manner proportionate to the
36
International Standards Organisations International Dictionary of Medicinal Products. An ICH workstream
that will set the harmonised international standards for medicinal product dictionaries.
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potential safety implications of the change. There has been some significant ground made in
consultation with the EMA on these points however the details are yet to be agreed and much
remains agreeable to both parties only in concept. With respect to the Roadmap for EVMPD EMA
has been enthusiastic to expand the database to included detailed substance information in the near
term. Industry are arguing again for a pragmatic approach, waiting for the IDMP implementation
guide (expected within about a year of IDMP standard finalisation) and allowing for an assurance of
quality data in what is currently available before further expansion.
Tasks and Responsibilities
As the policy lead for Article 57 I represented Pfizer on the EFPIA Temporary Working Group,
contributing to presentations, positions and communications. I also attended stakeholder meetings
with the EMA as an EFPIA representative and reported outcomes back into the Pfizer organisation.
Further to this I worked in close collaboration with Europabio to achieve harmonised positions and
gain additional allocation for Pfizer at the stakeholder meetings if required.
In collaboration with the operational team within WSRO responsible for managing the submission of
the information I built policy positions for Pfizer which were escalated to EFPIA. Through regular
interaction with WSRO and EU Qualified Person for Pharmacovigilance (QPPV) office developments
were monitored internally and required external communications agreed. At an above country level
I was the primary EU regulatory contact for the project and delivered several presentations and
communications to colleagues explaining the requirements placed upon Pfizer and the implications
to their working practice.
6a.ii Paediatrics
Introduction
The Paediatric Regulation (1901/2006 EC) was introduced in January 2007. It required that all new
medicinal products (Article 7) or existing products still benefiting from patent protection for which a
new line extension, indication or dosage form was being applied for (Article 8) must, where
appropriate, investigate its use in children (18). The requirement means it is compulsory to include
the paediatric data resulting from an agreed Paediatric Investigation Plan (PIP) before submission of
a MAA. A PIP is a research and development program agreed by the PDCO to ensure availability of
data in a paediatric population. Exceptions apply in the case of a deferral (typically, in appropriate
cases, until after studies are conducted in adults) or a waiver which is granted in circumstance where
product is non-applicable to the paediatric population. Following completion of all the measures in
the PIP and the registration of the resulting data by the EMA/EC or other competent authority
rewards (SPC37 extension) may be available.
Background
The regulation was introduced due to awareness that medicinal products were infrequently
sufficiently labelled for children. A lack of commercial incentive to specifically develop medicines for
children provided a population for which there was little knowledge in treatment effect. This
resulted in physicians prescribing medicines without a basis of data to support their safety and
efficacy in this population.
Children inherently metabolise medicinal products differently to adults and there are significant
variants depending on age and other developmental factors such as renal function. It is therefore
often inappropriate to prescribe a juvenile the same dose medication as an adult. HCPs were
unguided on the dose to be administered and so took varied approaches to treating paediatrics. The
37
Supplementary Protection Certificate – has an equivalent effect to extending the patent of a product.
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dangers of overdose or under-dosing and so diminishing the required therapeutic effect are
therefore increased.
The Issues
The problems experienced by Pfizer and the wider industry are in part due to the rigid nature of the
regulation which prevents the PIP procedure from being adapted on a case by case basis. There have
also been issues with the implementation of the legislation and the feasibility of some of the
requests made by regulators.

Highly detailed PIP submission early in Product Development: The regulation requires that
a PIP is submitted to the PDCO upon completion of pharmacokinetic studies in adults. With
some variability allowed in timing depending on the development process for the medicine
this is at an early stage of clinical studies when relatively little is known about the product.
The submission of detailed PIP therefore requires a level of assumption which frequently has
to be revised through a bureaucratic and resource intensive modification procedure.
 The Rushed Nature of the Procedure: Due to a poor format for interaction between
applicant and regulators there have been multiple case examples where outstanding issues
remain at the latter stages of the procedure. This leads to a period of frantic activity in which
alterations have to be agreed in the lead up to the final decision. As the timelines for
decision are set in legislation this has caused products to be withdrawn and resubmitted due
to insufficient time to make the required alterations.
 Divergent Global Requirements: The requirements for PIPs in the EU are poorly aligned with
the US, where for a start they submit much later. This prevents efficient paediatric
development on a global basis.
 Scope of Studies Requested by the PDCO: There have been occasions where the PDCO has
requested that sponsors undertake studies in therapeutic indications not intended for the
development of the medicine in adults. There have also been examples where the PDCO
have requested study designs which have been infeasible due to inability to recruit or
rejection of CTA at member state level.
 Applicability of the legislation to medicines developed for children: The regulation is poorly
designed to accommodate products which are intended primarily for paediatric use. This is
most common with vaccines and lead to a significant amount of activity at EVM (19).
Further detail can be found in the advocacy plan in annex II.
Pfizer has also experienced issues with the paediatric legislation Article 45 and 46, the requirement
to submit details of previously conducted studies in paediatrics (including those not conducted by
sponsor and literature review) and the obligation to submit study reports for paediatric studies
completed within six months of study completion respectively (18).
Advocacy Environment
The widely accepted view is that the Paediatric Regulation will not be revised in the 2014 review and
so advocacy activity has been fairly low in the last 12 months. In 2011 EFPIA published the results of
their paediatric survey aimed at highlighting some of the issues Industry experienced with the
implementation of the legislation (20). The themes have remained of concern with EMA providing
some proposed resolutions on certain points but these have not be satisfactorily implicated to date.
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The European Court of Justice ruling on the waiver application pertaining to Nycomed’s diagnostic
product Imagify backed the EMA in their refusal to grant a class waiver (21). This has been
considered by the EMA as support for them to request investigations into any indication which could
be of therapeutic benefit to children. The decision hinged on whether the EMA had the right to
determine how a sponsor developed a product. The implications of the judgement are to some
extent limited to diagnostics however the ripple effect spreads to therapeutics. The European
Ombudsman’s (EO) draft recommendation found the EMA guilty of maladministration in a separate
complaint procedure and has recommended measures been put in place focusing on increased
transparency of the PIP decision (22). The EO considered the PDCO opinion to be valid and
procedures followed correctly however they had failed to communicate the reasons for the decision
to the complainant. The EMA must respond in September 2012. The minutes of PDCO meeting in
June suggest that much more applicant data will be made publically available as a result of this
ruling. Further information on both of these topics can be found in the advocacy plan in annex II.
Tasks and Responsibilities
When I took on the topic the policy positions were not finalised. The first task was therefore to
determine the policy positions based upon Pfizer experience and get them endorsed through the
Paediatric forum. I gathered all possible product examples supporting our policy positions and
continuously updated these through the year. I monitored all available documentations on
developments on the topic and assessed the merit of Pfizer actions in these areas. For internal
communication I authored the paediatric Issue brief and Advocacy plan and gained endorsement for
the planned activities. I was heavily involved in the interpretation of the ECJ Nycomed judgement
and EO recommendation and provided internal briefs accordingly. I also lead the internal movement
on drafting a ‘template PIP’ for proposal to the regulators (see annexed advocacy plan and
Regulatory Rapporteur article), a work which is still in progress.
In response to an article in Regulatory Rapporteur, A TOPRA magazine, I authored and coordinated
the review process for an open letter response. The article featured was an interview of Dr Daniel
Brasseur, chair of the PDCO which addressed his views on some of the issues. The response was
designed to highlight the ideas which we appreciated and suggest ways of progressing for the
benefit of all stakeholders. The article can be found in annex II.
6a.iii Biosimilars
Introduction
Biologically similar medicinal products, biosimilars, are developed and authorised based upon a
comparison with the reference product. The concept behind their production is similar to that of a
generic product in as much as they copy the reference medicine and cannot enter the market until
the reference product has lost patent protection. However because of the sensitive nature of the
genetically engineered manufacturing process biosimilars will never be identical to the reference
medicine and therefore require more extensive development and proof of similarity than generics.
The assessment of biosimilars is a comparative exercise where quality, efficacy and safety are
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analysed. A biosimilar cannot be better or worse than the reference product to gain authorisation
based on an abridged dossier38.
Europe was the first region to establish a legal pathway for the authorisation of biosimilars and has
remained the leading region in the field. As a result many other markets reference EU policies,
legislation and guidelines. So far biosimilar medicines for filgrastim, somatropin and epoetin have
been authorised. Relative to other biological medicinal products they are relatively simple
medicines. The focus is now however moving to the more complex monoclonal antibodies (mAbs)
with one MAA submitted so far for a biosimilar herceptin.
Biosimilars currently have relatively low market penetration in many EU member states however
their uptake is increasing. This is driven by the cost containment policies adopted in response to
pressure from reduced national healthcare budgets. Biosimilars are marketed at a price reduction
relative to the reference product and the introduction of competition tends to reduce the pricing of
the originator. It should be noted however that, due to the complex nature of the products and the
high prices associated with biological medicines biosimilars remain considerably more expensive
than generics. The bigger pharmaceutical companies are investing heavily in biosimilars which is
seen as a significant market opportunity. This is partly based on a belief that the complex molecules
will be difficult for traditional generics producers to manufacture to consistent GMP standards,
making the peri-LOE space less congested. There are however many companies interested in the
field, the traditionally innovative like Pfizer, generics manufacturers such as Teva or Mylan, and
some unexpected players including Samsung.
The regulatory science of biosimilars is comparatively juvenile and highly dynamic. Several scientific
guidelines have been released or revised in the past year, the most prominent of which being the
mAb guidance released in June 2012. With a view to the future biosimilar developers and regulators
are considering the required methodologies to expand the potential of biosimilars. The two areas of
greatest focus are:


Extrapolation of Indications – Many of the biological products for which biosimilars are being
developed are authorised for multiple indications. There is an ongoing discussion between
stakeholders to decide what additional evidence is required to show that a product which is
biosimilar in one indication is also sufficiently similar in another indication for which the
reference product is authorised.
Proof of Interchangeability39 – At present it is not fully understood what level of evidence
would be required to show that the reference product could be interchanged with a
biosimilar (and in reverse) without influencing therapeutic effect. There are several schools
of thought on this matter, notably the FDA have suggested that switching studies would
likely be required. The EMA and within that the Biological Medicines Working Party
38
The biosimilar medicine relies upon the safety and efficacy data established in development of the reference
product. Therefore it has to show that it is “similar to” the reference product.
39
Interchangeability: where two products can be exchanged one with another without a significant risk of an
adverse health outcome. This term may be defined differently under different national laws.
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(BMWP)40 have been hesitant to engage with this topic as interchange-ability is not
incorporated in the marketing authorisation and the prescribing and switching of biosimilars
is an issue dealt with at national level in the EU. Industry is placing increasing pressure upon
the EMA to approach this from a scientific standpoint.
The Issues
The biosimilar environment is influenced by the range of industry players lobbying for the benefit of
their business plans. The policies of innovator only companies have a tendency to directly contradict
those of generics manufacturers as one group seeks to protect their products from competition and
the other to market such competing medicines. A sample of the issues are summarised here, further
details are available in the advocacy plan in annex II.
 Terminology: With the rapidly developing science new terms are being coined on a regular
basis. Some of the terms which are used by various stakeholders are also used for generic
medicines with a slightly divergent meaning. This has the effect of heightening confusion for
patients, prescribers and payors.
 Importation of Reference Product to EU: There is a legal obstacle which prevents the
importation of medicinal products for use in clinical trials from outside the EU without
providing a data package. The data required would not be available to the sponsor of the
comparative biosimilar/reference product trial and this prevents EU patients being included
when the reference product for the trial is sourced outside the EU. Industry has been very
strong in advocating for a work-around solution using bridging data which has been
acknowledged by regulators and the EC. The EC is said to be looking at the legal feasibility of
this approach.
 The Tajani Initiative: The Tajani Initiative comes from DG Enterprise and Industry at the
European Commission. The majority of its workstreams have a low level of activity however
the biosimilars workstream is an exception. The most important output from this initiative
will be a brochure designed to increase consumer confidence in biosimilars and drive
uptake. The Pfizer perception is that the EGA have been very successful in lobbying this
initiative however the innovative industry has started to provide a greater influence. The
result of this being that many of the details have to be omitted due to non-agreement.
Tasks and Responsibilities
I worked on this topic in collaboration with a colleague from the WRS Research Unit group who
specialised in biosimilars in the EU. The most frequent task was commenting upon various
documents produced by different stakeholders to ensure the Pfizer views were recognised. Policy
activity in this area has been very high during the past twelve months with many documents being
drafted by trade associations (both innovative and generic), the EMA and its scientific working
parties and the Tajani initiative. There was also a significant amount of activity outside Europe for
which I was involved in the compilation of comments. Other tasks included replacing the advocacy
plan which was out of date and no longer fit for purpose and producing a slide deck providing
training on the regulatory aspects of the topic for internal use. Providing competitive intelligence in
the field was a further function of my role, supporting both the policy arguments and Pfizer
biosimilar portfolio.
40
BMWP is a sub-committee of the CHMP responsible for authoring biological medicinal product guidance.
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6a.iv Others
Mediator
Mediator was a Servier product labelled as an add-on treatment for patients with diabetes who
were overweight. It was withdrawn from most major markets in the EU and US following safety
signals of heart valve damage and disease. The product remained available in France for nearly ten
more years before being withdrawn in 2009. One study estimated that the product was linked to at
least 500 deaths in France. The inquest that followed in France lead to a reorganisation of the French
national competent authority and it’s renaming as well as several changes to the legislation
governing pharmaceuticals in the country. In the wake of the affair the French agency has began to
re-evaluate medicines which have been on the market for at least 7 years or may have little
therapeutic effect. The estimated list of products is greater than 4,000 in total including many Pfizer
medicines. At a pan-European level the findings triggered a heightening of pharmacovigilance
measures in legislation which were rushed through with great urgency. It also lead to the removal of
the CHMP chair, Eric Abadie, after he was removed from the French NCA following an inquiry.
I maintained a watching brief on this topic, focusing on the pan-EU fallout. My main responsibilities
were monitoring developments in France, assessing the implications and communicating this within
the company. My main streams of communication were through articles in the Regulatory Policy
Newsletter and an Issue Brief which I updated in real time.
Information to Patients (ITP)
This was a proposal first brought forward by the EC in 2008 to allow Industry to provide more
information on their medicines to patients. The first proposal, drafted by DG Enterprise and
Industry41 was slammed for being too pro-Industry and blocked by the European Parliament. The
2011 proposal was more focused on patients needs however failed to navigate the political
minefield associated with the topic. This area requires a difficult balance as direct to consumer
advertising of prescription medicine is illegal in the EU. The amount of information available to
patients differs considerably between MS and the EC sought to improve the situation so that all EU
consumers could benefit from accurate, reliable information. The controversial proposal received
little support from stakeholders as Industry bemoaned the bureaucracy and member states were
concerned about the additional access pharmaceutical companies would have to patients. The
proposal stalled amidst opposition from Member states in Council who failed to reach a qualified
majority and was subsequently withdrawn. A further review of this legislation is unlikely to be
conducted for several years.
The majority of the advocacy work on this topic was conducted by the Government Affairs and
Public Affairs departments as the regulatory piece was small. There were, however some
pharmacovigilance measures attached to the proposal briefly following the Mediator fallout in an
attempt to rush them through the legislative procedure. When it became evident that the ITP
41
The Pharmaceutical sector was moved from DG enterprise and Industry to DG SANCO (Health and
Consumers) around the turn of year 2009-2010.
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proposal would be dropped they were split out from the legislation. I analysed the proposal for its
implications and provided internal communications for colleagues. These were in the form of an
Issue brief and newsletter articles.
Commercially Confidential Information
The EMA are taking steps to release a greater amount of previously confidential company
information and this trend is set to continue. The political pressure is in part derived from the
lobbying of academics who wanted the clinical data supporting the authorisation of medicines to be
publically available. In March 2012 the HMA/EMA released guidance on the classification of
information within the MAA42 as releasable, confidential (personal data or commercially sensitive)
and to be determined on a case by case basis. Simultaneously they opened a consultation on the
principles to be applied in the following of these guidelines. The consultation has been closed but
the final principles document is not yet available. It is the intention of the EMA to place the
releasable information upon their website for public viewing as soon as their IT infrastructure can
support it. More recently there are concerns that the European Ombudsman’s draft
recommendation to the EMA may mean a similar disclosure for paediatric investigation plans. Such a
move would require careful consideration as these are agreed prior to medicine authorisation and
so release of data may have much more significant implications for the company’s competitive
position depending on future circumstances.
Pfizer is supportive of increasing the level of transparency within the regulatory network as long as
the commercial interests of sponsors are protected. Much of the advocacy in this field is focused on
trying to improve transparency of the regulators procedures and some progress has been made here
with the EMA now publishing minutes for all the meetings of its scientific committees. Work is this
area involved commenting on the principles of releasing MAA information consultation, preparing an
issue brief on the guidance and communicating its implications to colleagues.
Medicines for Older People
In recent years the provision of medicines for the elderly has come under the political spotlight.
There has been mounting pressure from European parliament for legislators and regulators to
enforce that medicines are researched specifically with older patients in mind. This could provide for
more information on treating the elderly and potentially specific dosages for elderly people. It is
accepted that elderly patients are often excluded from clinical trials because of the complications
they bring to assessing the benefits of the investigational product, for example when they are taking
multiple concomitant medications. There is also the complication that chronological age is a poor
determinant of an individual’s response to medication. Typically renal or hepatic function is more
directly correlated to an individual’s metabolism of and tolerance to an active ingredient. There is
some movement from within the pharmaceutical Industry to introduce frailty as a determinant and
establish recognised endpoints associated with this. This is a direction being heavily advocated for by
Sanofi and GSK whom are both known to be developing medicines for Sarcopenia43 and are seeking
42
The guidance applies only to medicines which have been approved. Data for withdrawn and refused
medicines will not be published to the same extent as it may be commercially damaging if resubmitted at a
later date.
43
The degenerative loss of skeletal mass and strength associated with ageing.
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to ease the regulatory process and or benefit from any additional rewards which may be available
should a regulation akin to the paediatric regulation be brought into force. The EMA have taken, in
Pfizer’s view, a very pragmatic approach to the political storm to date.
The advocacy work has focused on ensuring the voice of trade associations is balanced and not
dominated by those companies seeking to develop medicines specifically for sarcopenia. From a
political standpoint it is important that the EMA, in collaboration with Industry, is seen to be working
on the issue to prevent escalation of pressure coming from quarters lacking the relevant expertise.
Pfizer is represented on the EFPIA TWG by a colleague from pharmaceutical sciences, who is an
expert on formulations. The hope is by advancing the development of age appropriate labelling and
formulations the situation can be improved without the enforcement of bureaucratic legislation. My
responsibilities in this area have been to provide this colleague with support on the more political
and regulatory matters. I have also contributed to Pfizer policies and comments provided on
external documents.
6b. Other Activities and Responsibilities
Pfizer Representative at Centre for Innovation in Regulatory Science (CIRS)
I attended a 2-day workshop of CIRS held in the UK focusing on their Quality Scorecard programme.
The aim of the programme is to create a scorecard to facilitate a numerical figure provided as
feedback of performance. It was designed as bi-directional process with regulators scoring applicant
submission and applicants scoring regulator performance. The discussions focused on balancing the
elements of the scorecard so that individual fields were weighed in correlation with their perceived
importance in provision of the overall results. To be successful in this role I had to familiarise myself
with the work done by the programme to date and query colleagues regarding their perceived
importance of the different factors prior to attendance. I provided a meeting report to feed back
into Pfizer and maintained contact with CIRS to follow up on their post workshop commitments.
EU Regulatory Policy Briefing
This was a new communication piloted early in my placement. I was tasked with designing our
newsletter and assumed the role of editor and coordinator throughout the year. The communication
aimed to share with regulatory colleagues the current policy topics, external triggers and
implications. It also provided a platform for EU regulatory policy to highlight some of its
achievements to the surrounding organisation. The newsletter was distributed to regulatory
colleagues in the country offices as well as above country regulatory strategists. An example issue
can be found in annex II.
EU Regulatory Policy Forum
I was tasked with coordinating the policy forum. This is a regular meeting including experienced
regulatory strategists and the EU country regulatory leadership team allowing in depth discussion of
specific topics used to help shape policy positions and gain new insights and ideas. Additional
members are invited on an ad-hoc basis dependent upon the topic. The presentation and chairing of
this meeting was shared within the EARP team on a topic dependent basis.
Regulatory Policy Global Alignment
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I inherited the role of coordinator for these meetings from a retiree within the policy group in
October 2011. There were bi-monthly telecoms in which the activity in the different regions was
informally discussed. A key objective of these meetings was to ensure that Pfizer’s external advocacy
worked as one voice and policies in the different regions were aligned. There are also insights to be
gained from the other regions as different sectors of regulatory science may develop at different
paces, or with different drivers. I also coordinated the face to face meeting held in Brussels which I
attended during which the aligned policy goals were determined and some key policy topics were
discussed in detail. A representative from EFPIA, new into a global policy coordination role was
invited to meet with us to explain her perspectives and objectives in the position. As is traditional for
this meeting I also organised a field trip to the European Parliament ‘Parliamentarium’, which turned
out educational for those of us living in the EU as well as US, resulting in a success.
Regulatory Policy Environmental Scan 2012
The environmental scan provides an overview of the external stimuli exerting an influence on the
regulatory environment. Updated on an annual basis the document provides internal stakeholders
with a summary of the issues and their implications. I was responsible for coordinating the drafting
of the document, authoring topics for which I was the lead, and providing a first review. The
document was distributed internally to WRS leadership, WRS-EU and country managers.
Sharepoint site Management
I was responsible for the maintenance and development of the EARP sharepoint site. This platform
allows important information to be shared with colleagues and archived in a secure manner.
Improvements included upgrading the navigation, adding additional information/webpages and the
addition of new features, for example the external event calendar which was designed to drive
collaboration between relevant colleagues.
Regulatory Strategy Support for CVMED portfolio
I provided strategic support for the filing of Eliquis in the EU, and preparation for a potential
Advisory Committee44 in the US. Eliquis is an anticoagulant for the treatment of venous
thromboembolic events. It is a direct factor Xa inhibitor. The major market opportunity is in the
prevention and treatment of atrial fibrillation. The accepted standard of care for these patients is
Warfarin which has a very well documented efficacy but is notoriously difficult to manage. Errors in
the management of Warfarin can be fatal and this deters many physicians. The alternative is Nonsteroidal anti-inflammatory drugs, most commonly Aspirin. These have a much reduced efficacy and
notable side-effects when maintained at moderate dose in the mid-term.
Eliquis, INN Apixiban, will be third to market in its class with Janssen Pharmaceutical’s Xarelto
(rivaroxaban) and Boehringer Ingelheim’s Pradaxa (dabigatran) already available. Despite this
competitive disadvantage clinical data supporting Eliquis is very strong and therefore it expected to
be successful. The support I provided focused on comparability exercises between the proposed
44
An advisory committee is a panel of external experts who provide their opinions upon the authorisation of
new medicines to the FDA. It is a public meeting used by the FDA to support their determination of the
Benefit/Risk balance of a product, and ultimately whether or not it should be authorised and with what
labelling to support its use.
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Eliquis labeling and the agreed labeling for the competitor molecules. I also analyzed the scripts of
the Advisory Committees conducted during the approval of the competitor molecules to highlight
potential issues.
Regulatory and Competitive Intelligence
In appropriate instances I provided intelligence support to regulatory strategists in certain fields. This
included for products related to policy priorities such as the Biosimilar portfolio. I also conducted
some market research associated with due diligence activities related to the in-licensing of products
in the gender health field where a significant co-pay product45 market opportunity was identified.
Clinical Trial and Regulatory Success Metric Analysis
In collaboration with the Regulatory Strategy Industrial trainee reporting into Speciality Care I led a
project analysing the regulatory output following the successful completion of a subset of clinical
trials. The trials used had been designed under a pilot project aiming to improve success rates. The
metric analysis we were provided with at outset showed that these trials had an increased success
rate by primary endpoint relative to baseline, and furthermore that the longer the project ran the
greater the percentage of success. The project was to analyse whether this apparent improvement
translated into regulatory success46. To determine this some key questions were identified, they
were;
 Was the clinical study report submitted in support of a regulatory claim47
 Did the submission gain approval
 How long did the process take48?
Because of the subjective nature of interpretation associated with many individual cases the
investigation had to be kept as binary as possible, allowing the identification of trends. The more
detailed reasoning for each case was collected where possible and archived as a resource for future
use in appropriate circumstances. Due to the size, and resource heavy nature, of the project we
prioritised the trials deemed most likely to have significant economic implications, specifically Phase
III trials. The project was designed to be passed on to the next years Industrial trainees for
continuation.
The initial results identified that the trends were less clear in terms of regulatory output than against
clinical trial endpoint. Some factors were identified as an influence in multiple cases. Overall the
data set was not large enough to drawn reliable conclusions at present however it did provide some
interesting insights.
People, Culture and Engagement
45
A product which is paid for, at least in part, by the patient as it will not be fully reimbursed. This is typical of
products associated with well being or appearance of well being.
46
Regulatory success was defined as gaining approval for the inclusion of wording in the label, upon which the
company could promote.
47
If approved, information upon which the company could promote the product
48
From top line report date (shortly after study completion) to submission, and to approval.
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The working environment of the Sandwich site, which was in the midst of widespread redundancies
when I joined Pfizer, was an area I considered I could positively contribute towards. I volunteered my
discretionary effort to workstreams focusing on fostering a productive, engaging and rewarding
workplace ethos. Key deliverables associated with this included the ‘Launch Event’ which coincided
with the consolidation of staff into three operating buildings and the ‘Sandwich Summer Fete’. I sat
on the planning team for these events and was heavily involved in this process. Both events were
widely recognised as resounding successes, contributing the reconstruction of a positive atmosphere
on the site.
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7. Placement Evaluation
Key learnings and experiences
This year spent on placement with Pfizer has contributed significantly to my professional
development and provided insights into the reality of employment within the pharmaceutical
industry. I have been able to garnish a top-line appreciation of the roles and functions of many
colleagues across the business and had the opportunity to become involved in a wide range of
projects. I was also provided with opportunities to represent the company externally and experience
interactions with regulators and trade associations which were a fantastic learning experience.
The focus of my work has been within the regulatory arena and it is here that I will take away the
most in-depth understanding.
I have worked with a wide variety of colleagues on a global basis in both small and large teams. I
have had to deliver to deadlines, to a high standard on a regular basis. My colleagues would also
expect me to provide a subject matter expert review on documents related to topics I worked on,
typically prior to external release. This was at first daunting however I became much more confident
in my own knowledge, and the value of my opinion where relevant, through the year.
Impression of the Industry
The simplest and possibly single most important question in this evaluation is would I now go on to
work in the Pharmaceutical Industry/for Pfizer? In short, I would very strongly consider it should the
opportunity arise.
It is very difficult to assess such a question without a suitable comparison however this placement
has not deterred me from following such a path. It is clear to me that there is a heavy pressure on
the sector to adapt and this will have significant impact upon employees.
Regulatory is a dynamic environment that requires constant learning. In conversations with many
colleagues one word that has never been used to describe the job is boring and this aligns with my
own experience. If I were to return to the field I would probably look for a role in policy (or other
above product function) or where the probability of working on products/indications pre-approval
was reasonably high.
Personal Development
There are many things I will take away from this placement that have a scope wider than the
workplace. My communication skills, particularly in terms of concise writing, have certainly
improved, as has my organisation, adaptability and confidence to implement my initiative. The level
of responsibility provided to me at times during my placement brought a degree of pressure but also
my best work, reinforcing my belief that I respond well to such situations.
I have been exposed to a wide variety of people, with different perspectives and from different
cultures; in circumstances I would not otherwise have seen. I was able to learn a lot from these
interactions about the working world, society outside it and myself.
It is my belief that few things are harder to grasp entirely than a perspective of one’s self in the
present and therefore I am certain the full benefit of the experience is yet to be realised.
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2. History of Pfizer UK. Pfizer.co.uk. [Online] Pfizer. [Cited: 09 07 2012.]
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3. Stevenson, Davina. What is Regulatory Affairs and why would I want a Career in it? The TOPRA
Guide to Careers in Regulatory Affairs. s.l. : TOPRA Publishing, 2010.
4. European Commission. Regulation (EC) 726/2004. europa.eu. [Online]
http://ec.europa.eu/health/files/eudralex/vol-1/reg_2004_726_cons/reg_2004_726_cons_en.pdf.
4.
5. European Medicines Agency. CHMP Rules of Procedure. ema.europa.eu. [Online]
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C500004628.
6. —. CHMP Workplan 2011-13. ema.europa.eu. [Online]
http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000095.
jsp&mid=WC0b01ac0580028c7a#.
7. —. About Us. ema.europa.eu. [Online] [Cited: 09 07 2012.]
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jsp&mid=WC0b01ac058001ce7d.
8. Heads of Medicines Agencies. Annual Report of the HMA Strategy. 2011-12.
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http://www.fda.gov/AboutFDA/Transparency/Basics/ucm192695.htm.
10. Elaine C. Esber, US FDA. Symposium on Global Drug Development Techniques - Bridging
Strategies. Kitasato University. [Online] [Cited: 11 07 2012.] http://www.pharm.kitasato-u.ac.jp/KH_sympo2000/esber.html.
11. European Medicines Agency. EMA Roadmap to 2015. ema.europa.eu. [Online] 26 01 2011.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000292.
jsp&mid=WC0b01ac05800293a4#.
12. Alex Philippidis, GEN insight and Intelligence. Euro Parliament Presses EMA on Curbing Conflicts
Despite Several New Measures. GEN - Genetic Engineering and Biotechnology News. [Online] [Cited:
23 07 2012.] http://www.genengnews.com/insight-and-intelligenceand153/euro-parliamentpresses-ema-on-curbing-conflicts-despite-several-new-measures/77899623/.
13. EMA. EMA Transparency Policy. ema.europa.eu. [Online] 19 06 2009.
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/10/WC500005269.pdf.
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14. European Commission DG Research & Innovation. FP7. European Commission, Research and
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European_Stakeholder_Model_ESM_Publication_June_2012-20120622-007-EN-v1.pdf..
18. European Commission. Paediatric Regulation 1901/2006 (EC). ec.europa.eu. [Online] 12 12 2006.
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Annex 1: Relevant Terms and Documents

(e)CTD – electronic Common Technical Document: An internationally agreed format for
applications to be submitted to the three ICH regions; USA, EU and Japan.
o In the EU the CTD is applicable to all procedures
Figure 14: Structure of the Common Technical Document (CTD)
CTD Structure
Module 1
Module 2
1.0 Regional Administrative Information
1.1 ToC of Module 1 or overall ToC,
including Module 1
1.0
2.1 ToC of the CTD (Mod 2,3,4,5)
2.1
2.2 Introduction
2.2
2.3 Quality Overall Summary
2.4 Nonclinical Overview
2.4
2.5
2.3
2.6
Module 3
Quality
Module 4
Nonclinical
Study Reports
2.5 Clinical Overview
2.7
2.6 Nonclinical Written and
Tabulated Summaries
Module 5
2.7 Clinical Summary
Clinical
Study Reports
2

Variations: Variation submissions are means of implementing changes to a products
regulatory profile. In the EU there are 3 major classifications of variations (all examples given
reflect Centrally Approved Products (CAPs):
o Type IA: Minor changes with minimal impact on quality, efficacy or safety. These are
reviewed by the EMA without the involvement of the rapporteur. The MAH does not
have to wait for approval to implement the change, “Do and Tell”.
o Type IB: Minor change which is neither Type IA or Type II nor an extension variation.
These are reviewed by the EMA (within 30 days) without the involvement of the
rapporteur. The MAH must wait for approval before implementation.
o Type II: A major variation which may have an impact on the quality, efficacy or
safety of the product. A formal review is required, normally involving the
rapporteur.

SmPC (Summary of Product Characteristics): Often referred to as the “label” this document
is agreed with the regulatory agencies. It is publically available and the principal material
referred to by doctors. The SmPC also provides the basis for promotional material delivered
to prescribers. Pharmaceutical companies are only allowed to promote their medicines
based on the wording agreed in the SmPC.
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
International Conference on Harmonisation (ICH): “ A joint initiative involving both
regulators and research-based industry representatives of the EU, Japan and the USA in
scientific and technical discussions of the testing procedures required to assess and ensure
the safety, quality and efficacy of medicines”. Key Achievements:
o
o
o
Common Technical Document
Guidelines
MedDRA: a global dictionary for medicinal substances. Codes defined by rules with
terms at different levels. This provides a tool for tracking adverse events.
Annex 2
A. European Parliament, Annex I and II, Reasons to Refuse the Marketing Authorisation
(Orphacol) European Commission and CHMP Opinion. Available from
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&frm=1&source=web&cd=4&ved=0CFM
QFjAD&url=http%3A%2F%2Fwww.europarl.europa.eu%2FRegData%2Fdocs_autres_instituti
ons%2Fcommission_europeenne%2Fcomitologie%2Fros%2F2011%2FD015522-03%2FCOMAC_DR(2011)D01552203(ANN1)_EN.doc&ei=wlP9T_wGxpmFB4OV8JQD&usg=AFQjCNGLabNvD8ZyeRF9ED0DAuNU
CpKnqw
B. EUCanANZ Regulatory Policy Environmental Scan 2012
C. Paediatrics Advocacy Plan
D. Regulatory Rapporteur Article (Published July/August 2012, pg 25) Ghost Authored: The
European Paediatric Procedure: An Industry Perspective – written in response to article: The
children’s advocate, May Issue of Regulatory Rapporteur.
E. Biosimilars Advocacy Plan
F. Example edition of EU Regulatory Policy Briefing (May 2012)
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