EU GMP Annexure -1 (Manufacture of sterile medicinal products) is ‘all set’ for revision

EU GMP Annexure -1 (Manufacture of sterile medicinal products) is ‘all set’ for revision

Annex 1, the primary GMP guidance on sterile manufacturing for Europe and PIC/S member countries is ‘ all set’ for revision . The original version was partially revised in 1996, 2003 and 2007. Proposed date for release of draft guideline is October 2015.

The current annex 1 will be revised to facilitate implementation of the principles in the ICH guidelines and to extend the underlying concepts to include new areas of technology and processing not previously covered and also to clarify areas that have been highlighted as ambiguous due to the age of the document.

The revised guideline will clarify to what extent Q9 and Q10 should be followed in the design and implementation of facilities, equipment and processes for the manufacture of sterile medicinal products. Other changes that may require new GMP guidance include those for the revision to the Ph.Eur. monograph on methods other than distillation for the production of water for injection.

The current guideline does not reflect the advances in the manufacture of sterile medicinal products; the revised guideline will embrace the use of new technologies

to prevent detrimental impact on product and also to encourage the introduction of new technologies that are not currently covered. The current guideline contains historical inaccuracies and areas of ambiguity, the revised guideline will correct the inaccuracies and offer more detail to remove ambiguity and to give clearer interpretation of GMP expectations.

Proposed timetable

Preparation of draft concept paper - September 2014

Approval of draft concept paper - October 2014

Released for consultation – February 2015

Deadline for comments – March 2015

Discussion in PIC/S Committee – May 2015

Discussion in GMDP IWG - June 2015

Discussion with other Working Parties - June 2015 – September 2015

Proposed date for release of draft guideline - October 2015

Deadline for comments - April 2016

Re - discussion in GMDP IWG - June 2016

Re - discussion in PIC/S Committee – July 2016

Important facts to be remembered about 21 CFR

Important facts to be remembered about 21 CFR

·       The Code of Federal Regulations (CFR) is an annual codification of the general and permanent rules published in the Federal Register by the executive departments and agencies of the Federal Government. 

·       The purpose of the CFR is to present the official and complete text of agency regulations in one organized publication and to provide a comprehensive and convenient reference for all those who may need to know the text of general and permanent Federal regulations.

·       The CFR is divided into 50 titles representing broad areas subject to Federal regulation. 

·       Each Title is divided into chapters that are assigned to agencies issuing regulations pertaining to that broad subject area. Each chapter is divided into parts and each part is then divided into sections -- the basic unit of the CFR.

·       Title 21 of the CFR is reserved for rules of the Food and Drug Administration. Each title (or volume) of the CFR is revised once each calendar year. 

·       A revised Title 21 is issued on approximately April 1^st of each year and is usually available several months later.

·         21 CFR Chapter 1 divided into following sub chapters

• ·               SUBCHAPTER A — GENERAL (Parts 1 to 99)

• SUBCHAPTER B — FOOD FOR HUMAN CONSUMPTION (Parts 100 to 191)
• SUBCHAPTER C — DRUGS: GENERAL (Parts 200 to 299)
• SUBCHAPTER D — DRUGS FOR HUMAN USE (Parts 300 to 370)
• SUBCHAPTER E — ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS (Parts 500 to 590)
• SUBCHAPTER F — BIOLOGICS (Parts 600 to 680)
• SUBCHAPTER G — COSMETICS (Parts 700 to 741)
• SUBCHAPTER H — MEDICAL DEVICES (Parts 800 to 898)
• SUBCHAPTER I — MAMMOGRAPHY QUALITY STANDARDS ACT (Parts 900 to 900)
• SUBCHAPTER J — RADIOLOGICAL HEALTH (Parts 1000 to 1050)
• SUBCHAPTER K — TOBACCO PRODUCTS (Parts 1107 to 1141)
• SUBCHAPTER L — REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION (Parts 1210 to 1272)

    Subchapter C divided in to following Parts

• PART 200 — GENERAL ( 200.5 - 200.200)
• PART 201 — LABELING ( 201.1 - 201.327)
• PART 202 — PRESCRIPTION DRUG ADVERTISING    ( 202.1 - 202.1)
• PART 203 — PRESCRIPTION DRUG MARKETING        ( 203.1 - 203.70)
• PART 205 — GUIDELINES FOR STATE LICENSING OF WHOLESALE PRESCRIPTION DRUG DISTRIBUTORS (205.1 - 205.50)
• PART 206 — IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE ( 206.1 - 206.10)
• PART 207 — REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL DISTRIBUTION ( 207.3 - 207.40)
• PART 208 — MEDICATION GUIDES FOR PRESCRIPTION DRUG PRODUCTS ( 208.1 - 208.26)
• PART 209 — REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO DISTRIBUTE A SIDE EFFECTS STATEMENT ( 209.1 - 209.11)
• PART 210 — CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL ( 210.1 - 210.3)
• PART 211 — CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS ( 211.1 - 211.208)
• PART 212 — CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY DRUGS ( 212.1 - 212.110)
• PART 216 — PHARMACY COMPOUNDING ( 216.23 - 216.24)
• PART 225 — CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS (225.1 - 225.202)
• PART 226 — CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES (226.1 - 226.115)
• PART 250 — SPECIAL REQUIREMENTS FOR SPECIFIC HUMAN DRUGS (250.11 - 250.250)
• PART 290 — CONTROLLED DRUGS (290.1 - 290.10)
• PART 299 — DRUGS; OFFICIAL NAMES AND ESTABLISHED NAMES (299.3 - 299.5)

Part 210 - CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL Sections: 210.1 Status of current good manufacturing practice regulations. 210.2 Applicability of current good manufacturing practice regulations. 210.3 Definitions.

Part 211 -CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Subpart A--General Provisions    § 211.1 - Scope.    § 211.3 - Definitions. Subpart B--Organization and Personnel    § 211.22 - Responsibilities of quality control unit.    § 211.25 - Personnel qualifications.    § 211.28 - Personnel responsibilities.    § 211.34 - Consultants. Subpart C--Buildings and Facilities    § 211.42 - Design and construction features.    § 211.44 - Lighting.    § 211.46 - Ventilation, air filtration, air heating and cooling.    § 211.48 - Plumbing.    § 211.50 - Sewage and refuse.    § 211.52 - Washing and toilet facilities.    § 211.56 - Sanitation.    § 211.58 - Maintenance. Subpart D--Equipment    § 211.63 - Equipment design, size, and location.    § 211.65 - Equipment construction.    § 211.67 - Equipment cleaning and maintenance.    § 211.68 - Automatic, mechanical, and electronic equipment.    § 211.72 - Filters. Subpart E--Control of Components and Drug Product Containers and Closures    § 211.80 - General requirements.    § 211.82 - Receipt and storage of untested components, drug product containers, and closures.    § 211.84 - Testing and approval or rejection of components, drug product containers, and closures.    § 211.86 - Use of approved components, drug product containers, and closures.    § 211.87 - Retesting of approved components, drug product containers, and closures.    § 211.89 - Rejected components, drug product containers, and closures.    § 211.94 - Drug product containers and closures. Subpart F--Production and Process Controls    § 211.100 - Written procedures; deviations.    § 211.101 - Charge-in of components.    § 211.103 - Calculation of yield.    § 211.105 - Equipment identification.    § 211.110 - Sampling and testing of in-process materials and drug products.    § 211.111 - Time limitations on production.    § 211.113 - Control of microbiological contamination.    § 211.115 - Reprocessing. Subpart G--Packaging and Labeling Control    § 211.122 - Materials examination and usage criteria.    § 211.125 - Labeling issuance.    § 211.130 - Packaging and labeling operations.    § 211.132 - Tamper-evident packaging requirements for over-the-counter (OTC) human drug products.    § 211.134 - Drug product inspection.    § 211.137 - Expiration dating. Subpart H--Holding and Distribution    § 211.142 - Warehousing procedures.    § 211.150 - Distribution procedures. Subpart I--Laboratory Controls    § 211.160 - General requirements.    § 211.165 - Testing and release for distribution.    § 211.166 - Stability testing.    § 211.167 - Special testing requirements.    § 211.170 - Reserve samples.    § 211.173 - Laboratory animals.    § 211.176 - Penicillin contamination. Subpart J--Records and Reports    § 211.180 - General requirements.    § 211.182 - Equipment cleaning and use log.    § 211.184 - Component, drug product container, closure, and labeling records.    § 211.186 - Master production and control records.    § 211.188 - Batch production and control records.    § 211.192 - Production record review.    § 211.194 - Laboratory records.    § 211.196 - Distribution records.    § 211.198 - Complaint files. Subpart K--Returned and Salvaged Drug Products    § 211.204 - Returned drug products.    § 211.208 - Drug product salvaging.