[Stability Testing related News – vol.18]

◆ Optimized Method for determining the Water Vapour Permeability for Packaging – new USP Proposal (03-Jun-15 ECA)

  In the Pharmacopeial Forum 41(1) a “stimulus to the revision process” article on pharmaceutical packaging has been published. This article proposes a new method for the determination of the permeability of water vapour for the General Chapter <671>.

The determination of the permeability rate for water vapour (“water vapour transmission rate”, WVTR) applies for solid dosage forms such as tablets or capsules that are packed in plastic bottles or blister packs.

The conclusion of the article is as follows:

WVTR can be measured by the weight gain of a desiccant or by the weight loss of water in a packaging system in an environment with constant temperature and relative humidity (RH). Packaging materials to be tested, which are filled with water, show a constant vapour pressure difference along the walls of the containers. This constitutes an improvement in comparison to the current WVTR testing according to <671>, in which the containers are filled with desiccant and where the vapour pressure inside neither starts nor remains at 0% rel. humidity.

When containers are filled with water,  many of the challenges can be avoided occurring with the use of desiccants and with the handling of containers which must be filled with desiccants – which is another advantage of the new method.

◆ WHO publishes interesting new Guidance for the Storage and Transport of Pharmaceutical Products (10-Jun-15 ECA)

  During The 137th World Health Organisation (WHO) Executive Board (EB) meeting, the Report of the 49th meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations was presented. With this report, a set of new guidances was adopted and recommended for use, in addition to certain monographs and general texts for inclusion in The International Pharmacopoeia. The report is now available in the WHO Technical Report Series as No. 992.

For those working in the area of Good Distribution Practice (GDP) the following paper might be interesting: Technical supplements to Model guidance for the storage and transport of time and temperature-sensitive pharmaceutical products.

This series of technical supplements intends to give further guidance and more details to the recommendations given in the Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products (WHO Technical Report Series, No. 961, 2011, Annex 9).This document focuses on principal requirements for the safe storage and distribution of time- and temperature sensitive pharmaceutical products (TTSPPs).

The additional documents are provided as supplements (see below) for a specific clause or clauses in the parent document mentioned above.

Supplement 1: Selecting sites for storage facilities
Supplement 2: Design and procurement of storage facilities
Supplement 3: Estimating the capacity of storage facilities
Supplement 4: Building security and fire protection
Supplement 5: Maintenance of storage facilities
Supplement 6: Temperature and humidity monitoring systems for fixed storage areas
Supplement 7: Qualification of temperature-controlled storage areas
Supplement 8: Temperature mapping of storage areas
Supplement 9: Maintenance of refrigeration equipment
Supplement 10: Checking the accuracy of temperature control and monitoring devices
Supplement 11: Qualification of refrigerated road vehicles
Supplement 12: Temperature-controlled transport operations by road and by air
Supplement 13: Qualification of shipping containers
Supplement 14: Transport route profiling qualification
Supplement 15: Temperature and humidity monitoring systems for transport operations
Supplement 16: Environmental management of refrigeration equipment

◆ MHRA informs about huge Counterfeit Case (01-Jul-15 ECA)

  The Medicines and Healthcare Products Regulatory Agency (MHRA) has published a press release about a huge counterfeit case. Fake medicinal products – worth 15.8 million British Pounds – have been seized in the UK. The seizure is the biggest recorded to date in the UK.

The operation called “Pangea VIII” was coordinated by Interpol and has lead to 156 individuals arrested worldwide. The majority of the products seized in UK originated from India, China, Hong Kong and Singapore. The medicines seized cover a wide variety of medicinal products. This shows again the importance of actions against counterfeit medicines. Just recently counterfeit products made their way into the legal supply chain in Germany.

The US FDA also took actions against the counterfeiters in this case. Moreover, even Google participated in the investigation from Interpol against the counterfeiters. This shows the dimension of the problem and the global impact. In the case from Indonesia for example, “authorities uncovered an operation where criminals were altering the expiry date or the amount of the active ingredient on packages of counterfeit, expired and unregistered medicines at the warehouse and returning them to a pharmacy for sale” (as reported by Europol).

◆ FDA Releases Long-Awaited Quality Metrics Guidance (27-Jul-15 FDA)

  The US Food and Drug Administration (FDA) released a draft guidance detailing how it plans to use quality metrics to improve its ability to conduct risk-based inspections and predict or mitigate potential drug shortages.

For the past few years, FDA has been considering measures to improve drug quality. In January 2015, FDA launched the Office of Pharmaceutical Quality (OPQ) with the goal of “creating a drug quality program as robust as the programs the agency already has in place for drug safety and efficacy.”

Part of the goal of creating the new office is to oversee drug quality throughout a product’s lifecycle, rather than focusing on pre- and post-market review. Through its surveillance, FDA says OPQ will be able to help the Office of Regulatory Affairs (ORA) “prioritize inspections … to try to mitigate quality problems before they lead to a recall or the need for an enforcement action.” This, the agency says, could prevent future problems, since “the majority of drug shortages stem from quality concerns.”

With the release of its new draft guidance, Request for Quality Metrics, FDA is giving more details to industry on its approach to quality metrics, as well as asking industry for its input in specific areas that are still being considered.

For companies with robust quality metrics data, this information could be used to “reduce the inspection frequency at an establishment.” In cases where the data raises issues, FDA says having the quality metrics data will allow it to “improve the efficiency and effectiveness” of the inspections. For now, the agency foresees its use of quality metrics to be used primarily for reducing inspection frequencies.

FDA says it will request the following 10 baseline quality metrics from companies as part of its analysis:

• The number of lots attempted of the product.
• The number of specification-related rejected lots of the product, rejected during or after manufacturing.
• The number of attempted lots pending disposition for more than 30 days.
• The number of out-of-specification (OOS) results for the product, including stability testing.
• The number of lot release and stability tests conducted for the product.
• The number of OOS results for lot release and stability tests for the product which are invalidated due to lab error.
• The number of product quality complaints received for the product.
• The number of lots attempted which are released for distribution or for the next stage of manufacturing the product.
• If the associated annual product reviews (APRs) or product quality reviews (PQRs) were completed within 30 days of annual due date for the product.
• The number of APRs or PQRs required for the product.

FDA is asking the public for comment on the draft guidance by 28 September 2015, and will be holding a public meeting on guidance on 24 August 2015.