Apotex Pharmachem Inc. Summary Report

Inspection Rating: Compliant

Company and Product Information

Apotex Pharmachem is a facility belonging to the Apotex Pharmaceutical Group of Companies. The facility is located in Brantford, Ontario, and conducts research and development activities, testing and active pharmaceutical ingredient (API) manufacturing activities. It manufactures twenty-eight (28) different commercial APIs for Canada, Australia, and other markets. APIs can be used in the manufacture of finished dosage form health products, or to compound medicines in pharmacies.

Background

Health Canada inspects facilities such as Apotex Pharmachem to verify compliance with the Food and Drugs Act and Regulations, which include internationally recognized Good Manufacturing Practices (GMP) standards. A plan is developed for each inspection based on information from a variety of sources including past inspections (by both Health Canada and other regulatory authorities), as well as quality and manufacturing documents specific to the facility to be inspected. Plans identify key areas for compliance verification based on risk.

One of the purposes of GMP standards and inspection activities is to identify areas that could potentially become safety issues before there is an actual problem with products on the market. But if safety issues are identified during an inspection that may pose an immediate risk to the health of the consumer, Health Canada takes timely and appropriate action.

Provided below is a summary of the July 2014 Health Canada inspection of Apotex Pharmachem in Brantford.

Planning for the Inspection

This was Health Canada's initial inspection of the Brantford facility related to its API activities. In preparation for the inspection, Health Canada inspectors considered the findings from a January 2014 U.S. Food and Drug Administration (FDA) inspection of an Apotex Pharmachem India Private Limited (APIPL) facility in Bangalore, India, that noted several significant deviations from GMP standards and concerns around data integrity. The FDA also inspected Apotex Private Research Limited (ARPL) in India in June 2014, which resulted in critical observations related to data integrity as well. Health Canada inspectors reviewed the company's corrective action plans and commitments made to the FDA at the time. With this information in mind, Health Canada's plan for the July 2014 inspection of the Brantford site included a focused review of lab data management practices.

Further to the Health Canada inspection, the FDA inspected Apotex Pharmachem in November 2014. Health Canada inspectors observed this inspection.  Some of the deficiencies noted by the FDA at the Brantford facility were similar to those identified by Health Canada. Health Canada and the FDA will continue to exchange information and results on the GMP practices of Apotex Pharmachem.

Summary of Observations

While the inspection did not identify any critical issues that required immediate action to help protect the health and safety of Canadians, it did identify 12 major observations and four other/minor observations that the company will need to address through its corrective actions in a timely manner and to Health Canada's satisfaction. Given the size of this facility, the complex nature of the work performed there, and the scope of the inspection, the number of observations was not unusual. None of the issues posed an immediate risk to consumers, but they are important points to correct to avoid potential risks in the future.

Data Integrity

Lab data management practices were one focus of the inspection. The testing lab was inspected with concerns regarding data integrity at the APIPL and ARPL sites in mind, but none of those issues were detected in Brantford. The integrity of the testing data is important because that testing is the basis upon which the API is released for further manufacturing into the health products used by Canadians and their families. Deficiencies were noted during the Brantford inspection with the management of electronic data, but there was no evidence of manipulation of data. For example, some instances of instrument use were not logged properly, and data from certain testing was misfiled.

"Out-of-specification" (OOS) results are test results that are outside the acceptable range, and GMP standards require an investigation into why these results occurred. All test results, including failures, should be tracked and considered when assessing the integrity of the product. It is important to determine if the test failed due to the product being faulty or because the instrument was used incorrectly. Deficiencies were noted at Brantford with the approach to handling OOS testing results. At the time of the inspection, the firm had also begun to implement a new approach to improving data integrity.

Cleaning

There were also a number of observations (five major, one minor) related to cleaning. A site's cleaning program and practices should be designed to minimize the possibility for product contamination. The observations included issues with the cleaning procedures, validation of the cleaning processes, and air quality monitoring. Other manufacturing control issues were noted that introduced the possibility of accidental mixing of API ingredients (cross-contamination). Any potential risks associated with these deficiencies were not considered to negatively affect the quality of the API produced in a significant way, and would not put consumers at risk. They will, however, need to be corrected.

Quality Systems

Quality systems activities such as training, handling complaints and self-inspection provide internal oversight of the firm's operations. They ensure staff is qualified to perform the required tasks and that there is a process in place to investigate complaints, which will help to identify the root cause of problems and immediately address them. There were no major observations made with most of the quality systems examined during the inspection. A lack of documentation to support the risk classification of high-risk materials was noted, however. This is important as staff need to know what products require special handling, and what controls must be in place to prevent any cross-contamination to protect staff and consumers who will eventually use the finished product. A risk-assessment tool was used to classify materials for containment purposes; however the criteria used for the determination were unclear.

Other Systems

Other issues were also noted with re-packaging operations not being performed according to Health Canada expectations, a lack of specificity in raw material sampling procedures, and deficiencies in temperature mapping of the areas where APIs are stored.

Next Steps

Apotex Pharmachem has been requested to provide corrective action information to Health Canada that outlines how it will address all of the issues identified at the time of the Health Canada inspection. Health Canada will actively monitor the implementation of the action plan at the Brantford facility.