FEEDBACK FROM
SAPRAA WORKSHOP
WITH PPB
DR DORCAS PETA
18 NOVEMBER 2011
QUESTIONS RECEIVED
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CTD
GMP Inspections
Analysis of Samples
Product Retention and Fees
Harmonisation
Medical Devices
Cosmetics and Complimentary Medicines
Other Questions
CTD Questions
• Summary Product Characteristics (SPC):
Here we normally refer to the attached
SPC. However, our agent was told by a
PPB representative that we cannot only
refer to the SPC, but need to provide a
summary of the SPC within the cover
pages of Module 1.
Response: Attach full SPC
CTD Questions cont.
• Our agent was told that we could not only refer to the
relevant overviews and summaries in the Body of Data
of Module 2, but that we had to provide actual
summaries of the QOS, Non-Clinical Overview and
Summaries, as well as Clinical Overview and
Summaries, within the Module 2 cover pages.
Response: Module 1 and 2 are required in word format and
have to be specific information for the sections within the
form. The reason is for the evaluators to make
comments during evaluation and create a report. Do not
cross reference.
CTD Questions cont.
• Should dossiers be completely converted from the old to
the new format when updating dossiers?
Response: If the registration is in the old format and is
concluded, can remain in that format until such time PPB
makes a decision. Industry has until December 2011 to
conclude all pending issues in the old format, other wise
the dossier will have to re-submitted in the new CTD
format.
• For products with different strengths, is it possible to
combine modules 3, 4 and 5?
Response: No. All the information to be included in each
strength.
CTD Questions cont.
• Which documents should be submitted in
electronic format? The complete dossier
(Modules 1 - 5) and in which format? Word
or pdf?
Response: 1 original hard copy and 1
electronic hard copy in PDF and Modules
1 and 2 in MS-Word, other sections in
PDF
CTD Questions cont.
• The application form – please advise the amount of
detail you want on it. Is it acceptable to put refer to?
Response: No. Specific information for Modules 1 and 2 to
be included in the form
• The numbering system in the application is different to
the CTD – would you accept if we sent a dossier with the
CTD numbering?
Response: Yes
CTD Questions cont.
•
Will it be acceptable to submit a Product Summary File
as per WHO requirement for a WHO prequalified
product. (vaccine)
Response: Yes, but applicant to use PPB form
•
Some vaccines were established many years ago
where there are no non-clinical data and in some
cases no characterization details / information
available as it wasn’t done, can we request exemption
for those parts.
Response: No. Applicant to generate the data, including
post surveillance data.
CTD Questions cont.
•
The query read thus: I have to respond to a resolution for a
product submitted in Kenya and our agent in Kenya has
suggested that we resubmit the entire dossier when we respond,
although only sections 18 and 19 will be updated (These sections
are the Bioavailability and Clinical sections in Parts XII and XIII
old format of application forms).
Response:
Submit full dossier mark the sections which have been changed.
NB: The deadline to submit queries from old dossier is December 2011,
after December applicants will be required to submit full dossier in
the new format
GMP Inspections cont.
• If the manufacturing site is FDA or PIC approved why is
it necessary for the PPB to also perform an inspection?
Response: Want to maintain ability to conduct inspections.
They will not perform paper evaluation
• Why doesn’t the East African Region share inspection
reports between the different Health Authorities?
Response: It is being looked into. There is lack of goodwill
from other HA to share the reports
GMP Inspections cont.
• What is the frequency of site re-inspections after
first approval?
Response: 3 years
• According to our agent, once the Inspection
form, SMF and payment have been submitted to
the PPB the onus is on the manufacturer to
ensure that an inspection is carried out at the
site.
Response: The applicant to follow up with PPB
GMP Inspections cont.
• The increase in costs from $500 every 5 years to
$300 every year we can live with, but the
additional costs like GMP inspection fees of
$4000 per site is just excessive. I also hear that
these GMP fees will also need to be paid every
3-4 years for the PPB GMP certificate to be
renewed.
Response: The fees are gazette into law. Yes,
applicants to pay re-inspection fees.
GMP Inspections cont.
• Are they actually going to inspect all the sites, and if so
how are they going to accomplish this with limited
personnel and in what timeframe. Could they not accept
GMP certificates from well established health authorities
or PIC countries. Is the EAC not now a PIC observer? If
this is to be introduced by 2012, how will they ever be
able to issue PPB GMP certificates for all manufactures
in time?
Response: PPB has enough staff complement to carry out
inspections. 15 inspectors for foreign inspections and 5
inspectors for local inspections.
GMP Inspections cont.
• Can they please extend the deadline for
applying for GMP certificates, which is required
when you apply for retention of the product.
Response: No registration until GMP inspection is
conducted. Applicant can appeal not to have
product pulled out of the market
GMP Inspections cont.
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If the product is a WHO pre-qualified
product will PPB still want to do a GMP
audit at the site of manufacturer already
audited and approved by WHO?
Response: Yes, according to the board, all
sites are to be inspected.
NB: SA is to be inspected in January 2012,
only if inspection fees are paid
GMP Inspections cont.
•
Some companies share a common
manufacturing facility, e.g. one manufacturing
site supplies product to four applicants. Must
each applicant pay the US$4000 GMP
inspection fee? Will it be acceptable for the
applicants to share the US$4000 (e.g. each
applicant pays only US$1000, or only one of
the four applicants pays the US$4000 in full)?
Response: Yes, companies can share costs
Analysis of Samples
• Pre-registration analysis of the product: Is
product analysis only valid upon first registration
of product in Kenya?
Response: No. There is periodic analysis. Kenya
has 3 laboratories approved by PPB.
Regarding testing of vaccines, the labs will
determine if they are able to test or not. If not,
the applicant can use an independent lab which
is WHO pre-qualified.
Analysis of Samples cont.
• Please clarify exactly which tests the Laboratory
is to carry out on the Drug Product. Will the
Laboratory carry out all the tests listed on the
CoA of the Drug Product or are there only
certain compulsory tests that need to be
performed?
Response: In some cases, some tests fail
therefore they would like to perform all the tests.
They test according to USP or BP monograph or
in-house method, whichever is filed.
Analysis of Samples cont
• The need to have all products tested at a local Kenyan
lab with new retention fees. Again this is a huge
additional cost and logistical nightmare for all applicants.
We have actually had cases where the labs have
returned tests that have failed, as they were in most
likelihood not performed correctly. When moved to
another lab they were fine. In many cases API standard,
reagents and columns may need to be provided and this
just escalates costs even further. If they do insist on this,
would they want the samples to be tested every year?
Response: No
Analysis of Samples cont
• Will the labs be able to cope with all the
new tests that need to be done?
Response: Analysis in not performed for
product retention.
Analysis of Samples cont
• Why are we required to submit samples when
applying for retention of a product. Why are they
refusing to accept samples labeled with S.A
label for these applications. Due to minimum
order quantities manufacturers are refusing to
just pack three samples for retention
applications.
Response: To ensure that product is the same as
in the market. Label has to comply with the PPB
requirements (e.g. mfg + exp. date required on
pack and this is not a requirement in SA)
Analysis of Samples cont
• Is there a reason why they don't want to accept
samples with 24 month shelf-life, when applying
for 36 month shelf-life. Because of minimum
order quantities can we be allowed to submit
registration samples with 36 month shelf-life
marketed in other countries (i.e. won’t comply to
PPB label requirements).
Response: We can submit samples with 24
months shelf-life with the corresponding stability
data up to 36 months. Label has to comply with
the PPB requirements
Analysis of Samples cont
•
Samples & Pre-registration Laboratory
analysis of the product sample – Our products
(vaccines) must be kept under cold chain
conditions i.e. -20 °C and between 2 °C – 8 °C;
must we submit the samples under cold chain
conditions and does PPB have the fridges to
keep the samples at recommended storage
conditions?
Response: Yes
Analysis of Samples cont
• 5g of active material for lab analysis is too much
especially for speciality products which are expensive.
Can the requirement be re-phrased to request enough to
do 10 runs?
Response: Dr Humphrey Mwavali to take this up with PPB
• Can the applicant request exemption on the number of
samples required for fridge items e.g. speciality
products?
Response: Yes, but must get an exemption letter from the
NQL in Kenya. The applicant may send the methods of
analysis to the lab prior to the application for the lab to
make the decision. If the lab grants the exemption, then
the applicant must submit 3 samples for evaluation with
the dossier application.
Retention fees
• Is the document on retention fees an
official guideline?
Response: The retention fees are gazetted.
SAPRAA to obtain a copy from PPB and to
distribute to members.
Retention fees cont.
• The new guideline for retention fee payment and
site inspection - is there a timeline when we
need to complete this task?
Response: Effective date is 1 August 2011.
Approved registrations prior to August 2011 are
valid for 5 years and no retention fee payments
during the period. Products registered after
August 2011, registration is valid for 1 year and
are subjected to annual retention fees payment
and site re-inspections if they do not have a
Kenya GMP Certificate which is valid for 3
years).
Retention fees cont.
• The 5 year registration renewal fee (US$500) has
apparently been replace with a US$300 annual retention
fee. Please confirm if this is true.
Response: Yes
• If the US$300 annual retention fee is applicable, then
does this mean that a renewal dossier is no longer
required?
Response: Yes
• Is it true that all the products registered with the PPB
must be tested annually by a Kenya laboratory? If this is
true, what are the requirements and how should one go
about to get your products tested?
Response: No testing is to be performed annually. One
sample is requested for the retention application
annually.
Harmonisation
• What progress has been made on the
EAC harmonisation initiative as far as
medicines registrations is concerned?
Response: Progress is very slow. They
share other information like counterfeiting,
benchmarking and product tracking.
Medical Devices
• Please provide an update on the status of
medical device registration in Kenya,
timeframes etc.
Response: Draft guideline out for comments
by January 2012. Previously medical
devices were regulated by Kenya Bureau
of Standards.
Cosmetics and Complimentary
Medicines
• What are the guidelines for Cosmetics and
Complementary medicines (herbals, Vitamins, etc)
Response: Guideline for complementary medicines only
• What is the review and approval process for these types
of products?
Response: 3 months to approve
• Is there a guideline or standard currently in place for
limits for ingredients in cosmetic products.
Response: No, currently cosmetics are regulated by Kenya
Bureau of Standards
Other Questions
• Can we have more than one agent in the
country provided they selling different products
e.g. one sells OTC and the other Pharma
products.
Response: No, only one Technical Representative
(RA agent) but can have more than one
distributor
• Does the PPB have variation guidelines as
currently there is nothing on the website.
Response: No. PPB is working on the guideline
and will be posted on the website before the end
of the year for comment.
Other Questions cont.
• Why are we required to pay for each
notification covered by one cover letter
(i.e. if there are five notifications then you
pay 5 x USD 200 = 1000), this was
according to our agent.
Response: Currently, this is correct.
Applicants to pay per change per product
but the guidelines are being reviewed.
Other Questions cont.
•
It is required to provide a Batch Manufacturing
Record (BMR) of a real batch manufactured
within at most six months before the
submission of the application. In some cases
the manufacturer do not want to provide this
document and state that it is available for
viewing by the National Regulatory Authority
(NRA) at the manufacturing site.
Response: This is acceptable
Other Questions cont.
• Is there an updated pharmacovigilance
guideline?
Response: Yes, on website.