Factorytalk publication in conjunction with CM Plus corporation (Japan)
Regulatory and compliance challenges for local and regional manufactures in the region
In general there are three types of players in the ASEAN regulated healthcare industries who have differing compliance concerns, for simplification we have named these; Locals, Regional Leaders and Multinationals. In the ASEAN region there are few Multinationals operating manufacturing sites with the exception of Singapore, which through aggressive targeting of the industry in providing heavy tax incentives has become the regional base for many of the Multinationals. Out of the other countries then Indonesia has passed legislation in order to require international Pharmaceutical companies to have an operations presence in the country and recently there are signs that point to the larger international and Japanese manufacturing firms returning to setting up facilities in ASEAN.
This article looks at the Regional Leaders:
These companies are ASEAN owned and much more externally driven and focused on growing overseas markets than their Local competition. All of these players grew strongly in their home countries and in some cases are competing on a large revenue basis, comparable now to international levels and the developed South Korean companies. As differentiation is important to becoming a leader at home and in new locations aboard then The Regional Leaders tend to specialize in more complex processes and dosage forms. Sterile products are typically produced by the more dynamic companies in ASEAN and their products are increasingly exported from the region to Europe, Japan and even the US. The Regional leaders must and do actively pursue standardization such as PIC/S compliance as this is their ‘passport’ to travel and a very important enabler of future growth both locally regionally and internationally. They consider that the playing field of standardization has yet to be leveled as many of their Local competition may not have invested as heavily in compliance as they have done, thus then often The Regional Leaders are pushing their respective Authorities to harden the application of regulatory requirements in audits and inspections. One of the key compliance needs for these companies is to have access to competent experts in their specialist areas, so there is a demand for international consultants to provide expert help that the Regional Leaders need in order to fulfill the newer GMP and technical requirements.
Key compliance issues and solutions
From the above simplistic overview of the ASEAN regulated industries then it is clear that the key compliance issues will vary based on the type of Player but in general and based also on recent inspection observations the following topics can be summarized and related to the ASEAN integration opportunities:
Basic infrastructure: facilities and utilities
The regional leaders have taken up and indeed powered the initiatives to comply with changing standards and many companies have had to build new facilities or heavily renovated their existing factories based on the PIC/s compliance requirements. This has resulted in a huge number of projects and initiatives in the region for the rebuilding and upgrading of facilities, utilities and equipment and these projects represent the majority of the investment costs and potential risk that the regional leaders have made. The Regional Leaders understand that it is vital that these projects are done using expert consultation to ensure that regulatory requirements and industry best practices are ‘built-in’ and that key aspects are not missed in the concept and basic designs and that sound project and validation management approach is followed throughout the entire project. Requirements for cross-contamination, cleaning, safety and exposure have been under constant change and if these and many other important topics are not covered successfully in the initial inputs to a large project then the large investments maybe wasted, losing valuable capital and time to correct and rework or in a worst case, rebuild!
The QA/QC groups are responsible in the organization to ensure compliance, so it is interesting that most observations and difficulties in inspection are related to the Quality Unit itself. Mostly inspections focus on the availability of, training on and adherence to the necessary documented procedures and processes. Many companies across ASEAN are struggling to fulfill what seems to be a heavy documentation burden related to compliance, often this is managed with a high overhead of people that must maintain the quality systems manually and inefficiently. Companies are not following the global trend of looking to technology as a short cut to ensure the basic document control, versioning, security, authorizations and timely review/approval functions that can be much more easily achieved electronically. The Regional Leaders have fast realized that PIC/s compliance requires many more records and controls. Batch records are still important but there many other individual documents needed for people, products and equipment covering all aspects of purchase, production, maintenance, labs, validation, dispatch, training, as well as audits, risk assessment and CAPA. The Regional Leaders are having to change their systems quickly to manage these records and training on best practice approaches to Quality Management is needed before making the critical adjustments to the Quality Unit and the quality procedures.
A large difference from the regulated industries in US/Europe to many countries across ASEAN is with the handling of the documents and the process of regulatory submissions and ongoing inspection. Some ASEAN countries are behind with regard to their management of regulatory submissions however Malaysia and Singapore in the region are once more leading the way with either fully or partly electronic submissions for applications and maintain proper ongoing changes to dossiers. One important standardization initiative that has been completed and is now in place throughout the region the ASEAN Common Technical Dossier (ACTD) format for the submission of regulatory documents. The ACTD format was intended to make the submission and approval process more efficient and to reduce work in making multiple submissions in several countries across ASEAN. Although currently there is no central application initiative then in the coming years it is expected that there will be further developments and country by country enhancements in the eSubmission space as the member nations implement new tools. For the ASEAN Regional Leaders then there are many challenges to navigate and understand the different regulatory requirements for example in the EU markets and in finding trusted partners for authorizations and distribution. Increasingly the Regional Leaders may look to setup their own operations overseas in important markets around the region and in the EU to better control and protect their products with their own staff to retain the market access knowledge.
Getting the best of IT projects
The Regional Leaders have traditionally used paper based systems for example for batch recording but this is now changing as organizations realize that to control critical data, documents and processes including all of the required corporate, production, labs and logistics information entirely electronically has tremendous benefits. The use of such systems needs to be balanced with the regulatory requirements to validate GxP critical systems that have an impact to patient safety and product quality and also the often under-estimated costs and timelines to implement what are often complex systems. ASEAN has a large talent pool of IT resources but their application in the regulated industries requires specialist and experienced skillsets, often the local integration and technology suppliers might not be familiar with the GxP aspects that must be designed into the projects and ensured by using software designed and suitable for the functions required. Many local ASEAN pharmaceutical companies are still using legacy and/or heavily customized software packages and therefore in the next year’s strong partners for IT compliance and implementation will be required and in demand across ASEAN. Coupled with the technical implementation skills than computer validation is required and must be applied in an efficient and effective manner to ensure that delivery of the solutions can be done on time and in budget.
Conclusions & Considerations
The huge change that ASEAN integration is bringing to the region is bringing difficulties for the Regional Leaders, however the opportunity and the realizable growth for products and new markets is clear and increasingly available to the more dynamic companies that are positioned to take advantage. The new projects that the Regional Leaders are undertaking to address these opportunities requires local and international experts with the relevant experience to help with the key decisions and help to manage the projects in the right way. Across the key aspects of facilities, utilities, production, and quality management then ensuring the right compliance requirements are built in at the beginning will maximize the benefit of the investment itself. The costs of the new investments that the Regional Leaders are making are such that the local demand for their products maybe now no longer enough and so a more integrated regional market is needed to sustain the growth of these Leaders. Several of the Regional Leaders are already exporting to the EU and Japan and looking now to the US as a viable future market.