In September 2013, the EU Good Distribution Practices (GDP) guideline for medicinal products became effective. Also in 2013, the Chinese FDA (CFDA) implemented their new Good Supply Practice (GSP) guidelines with the expectation that all Chinese drug distribution companies should be able to pass GSP certification after June 30, 2016.
Both of these new regulations are very similar in content and contain recommendations related to total supply chain risk aversion planning for all products covered under these guidelines. They also include specific supply chain management recommendations for cold chain and ambient products, with added directives and control initiatives aimed at preventing falsified medicinal products from entering the supply chain at any point.
The focus of both these regulation is on ensuring a secure supply chain with an aim to maintaining the quality, safety and efficacy of products from "source to patient."
Similarities in Supply Chain Guidelines
Quality Management System (QMS): Both require a fully documented QMS with a documented risk mitigation plan, appropriate and focused Standard Operating Procedures (SOPs) and Work Instructions (WIs) with a program for self-audits.
Personnel, hiring and training: Both require that all personnel hired have the background, qualifications and experience to perform the tasks they are hired for. Additionally, there should be ongoing training, and the European Union requires identifying a "responsible person" who manages compliance.
Documentation: Both require that all processes and procedures are documented, change control processes are in place and all documents are signed off to the appropriate level of authority—in the European Union, this includes the "responsible person."
Risk management: Both require drug distribution companies establish risk management plans and related SOPs.
Facilities: Both require conditions be maintained and monitored to ensure that products are stored and kept in conditions recommended by the manufacturers to maintain peak efficacy and quality. This includes cold chain, other controlled products, and products in quarantine. Both also define facility security and outline methods for preventing animals and bugs from entering the facility.
Transportation: Both require that medicinal products transported outside the controlled facility match the same environmental controls defined for their storage and these conditions are maintained until delivery to the patient.
Operations: Both include strict rules on where to obtain products, including approved packaging. Products can only be purchased via authorized distribution channels.
Complaints, returns, and suspected falsified medicinal products: Both require that all such products must be recorded and handled carefully according to written procedures, with records available for the appropriate authorities. All supply chain partners should have a consistent approach to controlling the entry of falsified medicines into the supply chain.
Outsourced activities: These should be correctly defined and controlled with a written contract outlining each party's duties. The services provider should have their own quality system in compliance with regulations subject to audit.
Sales and purchase records: Both require that accurate records are maintained for all sales and purchase transactions which match quantity, type of products (lot and serial number) and have the appropriate signatures from responsible parties.
Computerized systems and electronic data management: Both require drug distribution companies to implement strict management procedures for computerized data systems, in order to ensure data integrity and product quality.
Differences in Local and Global Impact
In regards to the local impact, the EU regulation clearly states that this will apply to any "actors" involved in distribution, wholesaling, and brokering of drugs—right back to the manufacturer, if they perform direct distribution of their own products.
Wholesale distribution activities are defined as including all activities relating to: procuring, holding, supplying or exporting (global impact) medicinal products. Therefore, the primary focus is on finished goods and patient protection.
It should be noted, however, that this regulation only applies to medicinal products, not APIs.
There are existing regulations within the European Union related to APIs requiring that these must have a certificate of authenticity and quality provided with them when shipped from countries other than Australia, Japan, Switzerland and the United States.
The new Chinese FDA regulation goes a lot further toward preventing falsified medicines from entering the supply chain by total verification of suppliers, review of vendor licenses, and documentation controls on what is ordered compared to what is delivered; in essence, a basic level of a "drug pedigree."
To this end, audits and compliance will be highly regulated under Article 79 of the Chinese Drug Administration Law that allows for heavy fines and potential loss of operating licenses for manufacturers, distributors, or wholesalers that do not comply.
Domestic API manufacturers within China do not need a GSP certificate to support API distribution. Foreign API importers will need a GSP certificate to support distribution.
Additionally, the Chinese GSP regulation has five annexes to address specific topics, two of which relate solely to temperature and humidity environmental monitoring for drug storage and shipment, including cold chain, or frozen drug storage, and transportation management.
Harmonization and Global Impact
Even though a life sciences company may be based in one region of the world, it is highly likely that they will ship products to different global locations. Therefore, with the new regulations being similar in content and structure, the approaches that global manufacturers, shippers and distributors implement for ensuring global compliance should be harmonized.
Within the European Union, there are 18 member countries that have accepted the new GDP regulations but may have slight variations on how they interpret compliance.
Raw materials and goods coming into the region from ICH countries, like Australia, the United States, Japan, etc., are exempt by the level of their own accepted standards and controls. But other regions exporting APIs and raw materials to the European Union will need a certificate of quality and authenticity, preferably from a regulatory authority.
Note: CFDA also requires that all API and finished drug importers should obtain an import license and submit the imported products for testing to be conducted at the Beijing, Shanghai or Guangzhou drug control institutes.
No matter what changes may be pending, or recently introduced, there are certain and basic key activities to ensuring compliance with all forms of global compliance. These are:
- Keeping up to date on new regulations
- Education and self-audits
- Maintaining a fully documented QMS—including a fully documented risk mitigation plan
- Appropriate staff training
These activities are recommended, at a minimum, for any medicinal product producer, warehouse operator, wholesaler or distributor that manages cold chain products.
About the Authors
Peter Norton is currently employed as the Business Development Director for DeltaTrak. He has had previous global program and project management responsibilities gained from advising clients on more efficient approaches to monitoring/managing cold chain logistics.
Ding Enfeng is currently employed as Vice General Manager for Shijiazhuang Lonzeal Pharmaceutical Company. He is in charge of Quality Assurance, the QC department, R&D and Materials Management.