[Stability Testing related News – vol.30]

◆  USP Draft General Chapters on Plastic Components and Systems Used in the Manufacturing of Drug Products (24-May-17 ECA)

The USP General Chapters—Packaging and Distribution Expert Committee proposes two new general chapters to address the qualification of polymeric components used in the manufacture of both pharmaceutical and biopharmaceutical active pharmaceutical ingredients (APIs) and drug products (DPs):

• <665> Polymeric Components and Systems Used in the Manufacturing of Pharmaceutical and Biopharmaceutical Drug Products;
• <1665> Plastic Components and Systems Used to Manufacture Pharmaceutical Drug Products.

The drafts of these two chapters have been published for public comment in Pharmacopeial Forum (PF) 43(3) [May–Jun. 2017]. Deadline for comments is July 31, 2017.

◆  The Association begins new work on medicines for children and better clinical trials and China Food and Drug Administration joins ICH (19-Jun-17 ICH)

The International Council for Harmonisation (ICH) met in Montreal, Canada on 27 May to 1 June 2017. Among other decisions, the ICH Assembly approved the China Food and Drug Administration (CFDA) as a new Regulatory Member, and Pharmaceutical Inspection Co-operation Scheme (PIC/S) as a new Observer. With these new parties, there are now 14 members and 23 observers, and full details are available on the ICH website www.ich.org.

◆  Being inspected by ANVISA? Or COFEPRIS? (28-Jun-17 ECA)

Most supervising authorities in the health care sector around the world have developed a regular inspection system to allow the periodic verification that a pharmaceutical manufacturer (APIs and medicinal products) does comply with the applicable GMP regulations. Although the idea and content of the GMP guidance is quite comparable, there is no common global GMP, and various inspectorates come and inspect facilities in other countries. The Brazilian ANVISA for example has published its own GMP Guidance.

The U.S. FDA is probably one of the most active agencies when it comes to inspections in other countries. But also inspectorates from other countries are coming to inspect, when a pharmaceutical product is intended to be imported. Two of those are for example the Brazilian ANVISA (Agencia Nacional de Vigilancia Sanitaria) and the Mexican COFEPRIS (La Comisión Federal para la Protección contra Riesgos Sanitarios – Federal Commission for the Protection against Sanitary Risk).

ANVISA Brazil

ANVISA requests certain pre-inspection information. A Brazil company representative has to request the inspection 6 months ahead of a license due date. On the ANVISA website, the Brazil legal representative completes and submits comprehensive information about the product and the manufacturing facility in a foreign country, including geographical coordinates and information about inspections by other healthcare agencies. In case of a certification renewal (which is every two years), ANVISA decides if another inspection will be needed based on a risk assessment.

ANVISA inspections are considered to be quite tough and strict. Inspectors focus a lot on the facility and operations. They want to be on the floor, when products are being manufactured. ANVISA inspectors prefer to perform multi-product inspections and are well trained, experienced and speak good English.

So what will they look for when they come for an inspection?

• HVAC systems and water treatment systems
• Quality systems
• Clearly defined validation guidelines and procedures (the “classical” approach with three consecutive batches is still expected)
• Involvement of (senior) management in the approval of SOPs, manufacturing documents and other documents
• Specifications and analytical methods
• Hygiene conditions
• Training of employees in production, quality control and quality assurance
• Demand for separate production lines for the production of human and veterinary medicinal products

At the end of the inspection, no report will be issued. But an inspection report must be generated within 30 days (the inspector does not decide how a defect is to be classified; this is decided after inspection within the authority). After a successful inspection, a GMP certificate will be issued.

COFEPRIS Mexico

COFEPRIS inspectors prefer to inspect the complete chain of a product with a tendency to longer lasting inspections (meanwhile at least seven working days). The inspectors work with a questionnaire which has to be completed. Amongst others, waste disposal, water supply and health monitoring of the personnel will be checked. Alike their colleagues from Brazil, COFEPRIS inspectors like to see on-going production processes.

The inspection report is prepared in Spanish during the inspection and must be signed by the company’s main contact partners on the last day of the inspection (every single page). So it is recommended to work with interpreters throughout the inspection.