Regulatory Updates In Brief

PIC/S GMP guide revised; EU GMP Annex 15 rewrite drafted; Reports OIG is preparing; Quality guidance FDA is drafting.

PIC/S GMP guide revised

The Pharmaceutical Inspection Cooperation Scheme, or PIC/S, said Jan. 31 it has revised its GMP guide effective March 1.

PIC/S said it introduced risk management principles into Part II of the GMP Guide, which corresponds to the International Conference on Harmonization Q7 GMP guideline for active pharmaceutical ingredients.

PIC/S said it also revised some of the annexes, though not Part I of the guide.

PIC/S revised Annex 2, which concerns biological drug products. Part A of the revised annex provides supplementary guidance on manufacture of biological medicinal substances and products, while Part B adds further guidance on specific types of biological medicinal substances and products.

PIC/S also revised Annex 14 for manufacture of products derived from human blood or human plasma – and added an annex on radiopharmaceuticals to its guide on preparing medicinals in healthcare establishments.

EU GMP Annex 15 rewrite drafted

The European Commission Feb. 6 published a draft revision of Annex 15 of the European Union GMP Guide, which concerns qualification and validation.

Comments are due May 31 on the draft, which takes into account changes since the current version was published in September 2001 to other sections of the EU GMP Guide, the International Conference on Harmonization Q8, Q9, Q10 and Q11 guidelines and Quality Working Party guidance on process validation, as well as changes in manufacturing technology.

PharmOut Pty Ltd., Melbourne, Australia, has published an analysis of the draft that emphasizes its incorporation of the three ICH guidelines and the related concept of knowledge management, as well as its adoption of the lifecycle approach to validation and qualification activities.

Industry has been encouraging European authorities to update guidance in line with the transition over the past decade from retrospective to lifecycle validation (Also see "Industry Urges EU to Align Draft Validation Guidance with ICH and FDA" - Pink Sheet, 25 Jan, 2013.).

Upcoming OIG reports

The Health and Human Services Department’s Office of Inspector General is working on several reports in the pharmaceutical arena that it expects to publish before October.

The office is reviewing FDA’s oversight of generic drug manufacturing operations. It will describe the extent of the agency’s inspections and the results in terms of enforcement actions taken in response to shortcomings and deficiencies.

The office is examining the Medicare program’s oversight of pharmaceutical compounding in acute care hospitals in light of the recent fungal meningitis outbreak that resulted from injection of contaminated compounded drugs (Also see "A Lesson on Outsourcing: The NECC Fungal Meningitis Outbreak" - Pink Sheet, 29 Nov, 2012.).

The office also is reviewing efforts by the Center for Disease Control and Prevention to secure pharmaceutical stockpiles from theft, tampering or other loss. FDA periodically approves shelf-life extensions of drugs in the stockpile.

FDA drafting quality guidance

Several guidance documents FDA’s Center for Drug Evaluation and Research plans to draft this year stem from additional requirements in the Drug Quality and Security Act of 2013 (Also see "Drug Manufacturers Get the Anti-Counterfeiting Law They Wanted: Now They Must Meet Deadlines" - Pink Sheet, 19 Dec, 2013.), according to a list the agency published Jan. 31.

There are two related to the legislation’s anti-counterfeiting provisions – one for identifying suspect product and the other for exchanging information to trace drug products through the distribution chain. There also is one related to the legislation’s provisions on drug compounding that concerns user fees for the new FDA-regulated category of compounding outsourcing facilities.

In the quality category, the agency is working to propose guidance on:

• Contract manufacturing quality agreements;
• Good manufacturing practices involving cloud computing;
• Interim GMPs for the category of FDA-regulated compounding outsourcing facilities established under the Drug Quality and Security Act of 2013;
• The quality systems approach to drug GMPs; and
• Submission of Field Alert Reports and Biological Product Deviation Reports;

In the chemistry category, there are eight, including guidance on:

• Chemistry, manufacturing and controls information in comparability protocols;
• Validation of analytical procedures and methods for drugs and biologics; and
• Allowable excess volume and labeled vial fill size, which is noteworthy given the recent spate of recalls of incorrectly filled vials and cartridges, including 2.5 mL cartridges labeled for 1 mL (Also see "Drug Product Recalls in 2012 Categorized by Problem Area" - Pink Sheet, 30 May, 2013.).

There are also going to be several draft guidance documents for electronic regulatory submissions, including manufacturing establishment information.