Understanding CGMPs –
What Attorneys Need to Know
The Nuts & Bolts of CGMPs:
FDA Guidance for Industry
Paula R. Katz
Acting Branch Chief, Regulatory Policy and Collaboration
CDER/Compliance/Office of Manufacturing and Product Quality
July 10, 2013
Objectives
• Brief background
– Where do guidance documents fit into the
regulatory scheme?
– What are the types of guidance documents?
• CGMP Guidances
– Practical matters
– Recent GFIs
– ICH “Q” documents
• Help!
Admin Law 101
• Congress says what is mandatory in the
FDCA (or PHSA, etc.)
• Secretary (FDA) promulgates regulations
that indicate details about what is required
by the Act (21 CFR 210 & 211, 600s, etc.)
• Guidance documents describe FDA’s
current thinking on a particular topic
– Not binding on FDA or any party
Types of Guidances
• GGPs (21 CFR 10.115) establish 2 types
• Level 1:
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–
–
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First interpretations of statutory or regulatory requirements
Changes in interpretation or policy (not minor in nature)
Complex scientific and highly controversial issues
May solicit public input before issuance, but comments can
be submitted at any time
• Level 2:
– Existing practices or minor changes in interpretation or
policy
– Level 2 guidances post directly to the internet
Documents that are not
“Guidance for Industry”
(but we know you look at them)
• Compliance Policy Guides (CPGs)
– advise field inspection and compliance staff on
standards and procedures for determining industry
compliance
http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/default.htm
• Compliance Program Guidance Manuals (CPGMs)
– instructions to FDA staff for obtaining information to
help fulfill agency plans in the specified program
areas
http://www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/default.htm
Some Practical Matters
• All Human Drug GFIs on the web at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
– For CGMP GFIs, click “Current Good Manufacturing Practices
(CGMPs)/Compliance”
– Don’t forget about International Conference on Harmonisation
(ICH)-- especially the “Q”s (more later)
• Guidance Agenda:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UC
M314767.pdf
• Comments:
– You can comment on any guidance at any time.
– Especially for drafts, submit electronically at www.regulations.gov
Recent CGMP Guidances*
• Heparin for Drug and Medical Device Use:
Monitoring Crude Heparin for Quality
(06/25/13)
• Contract Manufacturing Arrangements for
Drugs: Quality Agreements (Draft 05/24/13)
• Non-Penicillin Beta-Lactam Drugs: A
CGMP Framework (04/17/13)
*Excludes PET drug guidance documents and ICH documents
Heparin for Drug and Medical Device Use:
Monitoring Crude Heparin for Quality
• Final Guidance published June 25, 2013
• Purpose: help manufacturers prevent the use of
crude heparin that might contain over-sulfated
chondroitin sulfate (OSCS) or non-porcine
ruminant material contaminants
Contract Manufacturing
Arrangements for Drugs:
Quality Agreements
• Draft Guidance published May 24, 2013
• Comment period closes July 29, 2013
• Purpose: describe how Quality Agreements
can be used to define, establish, and
document the responsibilities of each party
contract manufacturing of drugs
Non-Penicillin Beta-Lactam Drugs:
A CGMP Framework for Preventing CrossContamination
• Final Guidance published April 13, 2013
• Second of three planned guidance documents
on cross-contamination
• Purpose:
– explains health risk from cross-reactivity in defined
classes of sensitizing beta-lactams
– promotes use of dedicated facilities/equipment
Other GFIs
•
•
Pyrogen and Endotoxins Testing: Questions and Answers (06/28/12)
Questions and Answers on Current Good Manufacturing Practices (CGMP)
for Drugs
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•
•
•
•
L2 Guidances; most recently updated12/21/11
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm124740.htm
Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products
(5/4/2011)
Process Validation: General Principles and Practice (01/24/11)
Use of Mechanical Calibration of Dissolution Apparatus 1 and 2 (01/26/10)
Pharmaceutical Components at Risk for Melamine Contamination
(08/06/09)
Current Good Manufacturing Practice for Phase 1 Investigational Drugs
(07/14/08)
*Excludes PET drug guidance documents and ICH documents
Other GFIs
• Testing of Glycerin for Diethylene Glycol (05/01/07)
• Investigating Out-of-Specification Test Results for
Pharmaceutical Production (10/11/06)
• Quality Systems Approach to Pharmaceutical Current
Good Manufacturing Practice Regulations (09/27/06)
• PAT—A Framework for Innovative Pharmaceutical
Development, Manufacturing, and Quality Assurance
(09/29/04)
• Sterile Drug Products Produced by Aseptic Processing
— Current Good Manufacturing Practice (09/29/04)
*Excludes PET drug guidance documents and ICH documents
ICH Q7 and APIs
• All drugs are subject to CGMP under FDCA 501(a)(2)(B); no
distinction between APIs, excipients, or finished pharmaceuticals
• 21 CFR 210 & 211 apply to finished pharmaceuticals; FDA has not
promulgated CGMP regulations specifically for APIs
• FDA has long recognized that CGMP requirements in Parts 210 and
211 are valid and applicable in concept to API manufacturing
• Principles include, but not limited to:
– building quality into drug by using suitable equipment and employing
appropriately qualified and trained personnel,
– establishing adequate written procedures and controls designed to
assure manufacturing processes and controls are valid,
– establishing system of in-process material and final tests
– ensuring stability for intended period of use
ICH Q7 and APIs
• In 2001, FDA adopted an internationally
harmonized guidance to industry on API
CGMPs in conjunction with regulatory
partners in the International Conference
on Harmonization of Technical
Requirements for Re gistration of
Pharmaceuticals for Human Use (ICH)…
That’s a long way to say, “ICH Q7”
•
ICH Q7 represents FDA’s current thinking on CGMPs for APIs
•
Remember—no CGMP regulations for API, so…
•
API and related manufacturing and testing facilities that follow ICH Q7
generally considered to comply with statutory CGMP
– alternate approaches may be used
– requirements of 501(a)(2)(B) can be met if approach ensures that API meets its
purported or represented purity, identity, and quality characteristics
•
ICH Q7 and other ICH guidances on the web at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065005.htm
•
Especially: Q9 Quality Risk Management & Q10 Quality Systems
– See also: Q8 (development of product) and Q11 (development of APIs)
– You might hear “drug substance” instead of “API” when dealing with FDA reviewers
You’ve Got Questions?
We’ve Got Answers!
• CGMP Subject Matter Contact List
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedic
alProductsandTobacco/CDER/ucm096102.htm
• Paula Katz
Paula.Katz@fda.hhs.gov
301-796-6972