By Sharon Johnson
Pharma firms must ensure that all outsource providers’ locations have a robust and consistent quality management system.
An effective strategy for partnering with a global outsourcing organizationOn Aug. 6, 2009, U.S. Food and Drug Commissioner Margaret Hamburg, MD, made her first presentation to the Food and Drug Law Institute, announcing a new enforcement policy to ensure regulatory compliance in the pharmaceutical and biotechnology industry. Dr. Hamburg stated that in order for the U.S. Food and Drug Administration (FDA) to be a strong agency—one the U.S. public can count on—the agency must appropriately enforce laws to assure that only safe and effective medical products are introduced into the marketplace.
One theme Dr. Hamburg stressed was that this new policy applies not only to the drug/biotech applicant owners but also to the outsourcing companies with which they work. Both the pharma/biotech company and the outsource organization are inspected by regulatory agencies and must have equal understanding of all relevant current good manufacturing practice (cGMP) requirements.
Now, more than a year since Dr. Hamburg’s address and at a time of potential growth in outsourcing, it is timely to consider the relationship between the pharma/biotech applicant holder and its outsourcing partners with regard to cGMP compliance and the FDA 2009 enforcement policy, as well as regulatory agencies around the world. This article examines a standard way of working between the applicant holder and the pharma/biotech outsourcing company to ensure a mutually successful relationship of cGMP/policy compliance. The pharma/biotech company is referred to as the contract giver, and the outsourcing company is referred to as the contract receiver.
In the 2010 Annual Outsourcing Survey of more than 350 sponsor-side respondents, 44% reported that their outsourcing spending grew in the previous year (2009), and 45% projected that it would grow in 2010.
The 2009 growth was primarily experienced by Big Pharma (28%), followed by small/mid-tier pharma (16%) and virtual pharma (15%). Of the companies that outsource at least half of their commercial manufacturing, 59% outsource to preferred providers, 78% have never received a warning letter due to an inspection, and 81% would describe their relationship with a provider as a partnership. Nearly half (47%) of the companies said more than half of their outsourcing is with preferred providers.
Many organizations view the use of outsourcing organizations as an approach to driving efficiency, so it should come as no surprise that the practice is becoming more common.
Pharma/biotech companies must ensure that all their outsource providers’ locations have a current, robust, consistent quality management system (QMS) program in use. Even those contractor sites not used by the applicant holder must have an excellent compliance program, because the regulatory outcomes of any one of the contractor’s sites have the potential to affect all the contractor’s sites, and, consequently, the pharma/biotech applicant holder.
Companies are coping with change, including cost pressure, consolidation, loss of patent protection, the uncertainties of healthcare reform, increased Phase IV and comparator studies, and heightened regulatory oversight. As a result, the pharmaceutical industry is trending toward greater use of outsourcing, using a few key preferred providers as partners.
It is incumbent on the contract giver to thoughtfully evaluate the contract receiver’s critical thinking and escalation process in light of regulatory expectations for worldwide compliance.Following Dr. Hamburg’s expectations and the requirements of other worldwide regulatory agencies, the applicant holder’s expectation of its outsourcing contractor should be one consisting of a strong collaborative relationship with strategic partnering to ensure safe and effective drug products and excellence in compliance. This article focuses on effective ways for pharma/biotech and contractor partners to work together to ensure the highest level of compliance, with the partnership creating positive results for both parties.
Work EffectivelyThis section describes an industry standard for contracting with an outsourcing organization that encompasses both the contract giver and contract receiver. Such a standard will promote best practices and high-quality end products consumers can trust.
There are three components essential to ensure a strong partnership between the contract giver and contract receiver. Excellence in cGMP compliance will be attainable and sustainable if these practices are followed:
- Select a highly qualified contractor (e.g., a contractor who understands, implements, and sustains cGMP compliance with the latest in regulatory expectations).
- Develop a clear partnership arrangement in which both parties understand what being a partner means and what it takes to develop an effective partnership, including trust and constant communication regarding the expectations of both sides.
- Establish a process that instills the ability to think forward, with both partners not only agreeing on the current interpretation of a regulatory/compliance requirement but also collaborating to anticipate the next steps needed to ensure continuous improvements, the partnership’s standard way of working to ensure success.
Six Steps to Improve Compliance Preparedness
- Improve operating systems, management systems, and behaviors;
- Partner with an outsource organization in whose quality of work and data you have complete confidence;
- Ramp up automation to enhance efficiency;
- Increase frequency of quality checks;
- Institute more efficient corrective action; and
- Maintain a current, robust, and consistent QMS program.
Select a PartnerSelecting the right partner is one of the most critical decisions necessary to ensure a successful business outcome. To understand the term partnership and its application in the pharma/biotech space, there are important quality and regulatory compliance considerations that must be evaluated by both the contract giver and the contract receiver.
The contract giver must have a clear, comprehensive, easily understood contracting program that assures confidence in the outsourcing partner. The contract receiver must have confidence in the contract giver’s requirements, and should fit or comply with the contract giver’s business plan and not be in conflict with its overall quality program so as to maintain a compliant, sustainable business. The selection process for each party should include a due diligence program that covers critical quality and compliance factors before work begins and should continue throughout the work cycle between both parties. Due diligence becomes the standard work practice, in which evaluation with continual feedback is a routine process.
The contract giver’s due diligence program should assess regulatory compliance factors, such as the contractor’s QMS and the knowledge and experience the contractor brings to the work to be performed. The contract receiver should provide staff with sufficient education, knowledge, and experience in the industry to perform their associated tasks.
In the due diligence process, the contract giver will expect complete transparency from the contract receiver as a standard way of working. One of the most important factors in the due diligence process is assessment of the transparency the contractor provides regarding all facets of regulatory compliance processes, metrics, and action plans for continuous improvements through corrective actions/preventive actions (CAPA). This sharing of details is of the utmost importance for both parties and should be done as standard practice to assure that the right metrics are being evaluated and a trusted partnership has been established.
Another quality to expect from the contract receiver includes a satisfactory regulatory compliance history from worldwide agency inspections and a high level of regulatory intelligence. The contractor should have a thorough understanding of the complex, ever-changing regulations around the world, understand the impact a change to cGMP regulations or new guidance would have on the product, and be able to offer solutions to ensure continued compliance. It is incumbent on the contract giver to thoughtfully evaluate the contract receiver’s critical thinking and escalation process in light of regulatory expectations for worldwide compliance.
The selection process should address how communications will take place between the contract giver and the contract receiver’s various sites. The internal communications within the contractor’s multiple sites, which may be worldwide, must be a key factor in such processes as complaint handling and change control. The contractor’s metrics for continuous improvement and the system used to report back to the contract giver’s business are critical for long-term success. The communication systems must incorporate a quality agreement to ensure proper responsibility, and accountability must be made known throughout both organizations.
A Partnership Strategy for Optimal Compliance
Table 1. Examples of the QMS program include global standards for the following:
- Corporate quality policies, standards, and standard operating procedures (SOPs);
- Business unit and site-specific SOPs;
- SOP for investigation handling and root-cause analysis;
- Internal audit program with dedicated staff;
- CAPA system;
- cGMP training programs;
- Process for regulatory actions such as field alerts or product recall, including reviews at all sites for effectiveness evaluations of CAPA and best practices results sharing;
- Response to regulatory agency observations;
- Batch records not right first time;
- Response to contract giver’s audit observations, shared throughout the organization for CAPA and best practice sharing;
- Lean processes and tools, Black Belt staff;
- Supplier-management program; and
- Quality agreements (customer and supplier).
In a recent 12-month period, Catalent underwent 52 inspections from 20 global regulatory authorities. It is common to average more than 20 customer audits within a single month. Catalent employs a robust process for partnering with the pharma/biotech industry. This partnering includes a transparent QMS program, pro-active outreach to customers, and participation in setting future standards and guidance for the industry.
Transparent QMS Program Catalent’s process for partnering is a QMS program that includes high-level policies and standards driven by global working groups as well as site-specific standard operating procedures to ensure enactment of the corporate programs. Advanced electronic tools are used throughout the company for consistency.
The QMS is a continuous, proactive, and interactive program of improvement to strengthen current processes. The QMS is coordinated from a central quality organization with staff strategically based throughout Catalent sites.
This central function provides an internal audit program, supplier-auditing program, and cGMP training that includes root-cause analysis, and provides for cross-functional ways of working within Catalent’s current quality, safety, and operations. It shares performance metrics with customers, including specific metrics around their products, as well as Catalent’s compliance improvement initiatives. Examples of the Catalent QMS program of global standards can be found in Table 1.
Catalent’s ApproachDaily: Cross-functional management teams walk the production floor every morning and review critical site quality and operation metrics—the daily stand-up. The team analyzes the most current input and status of operations and issues, acts on opportunities for improvement with site owners and timelines, and determines actions needed to mitigate risk. The site-management team reviews current metrics such as complaints, process delays, deviations/investigations, and safety issues. This floor review involves operations, warehouse, quality, and safety for the most current assessment of Catalent’s internal work processes/practices.
Monthly/quarterly: Catalent works with customers through routine face-to-face meetings to cover quality and operational business. The agreed-upon metrics are reviewed, and highlights of corrective/preventive actions (CAPA) are covered, as well as future recommendations for continuous improvement. The senior-most level of Catalent leadership is involved in the customer discussion and helps drive the partnership toward mutually beneficial outcomes. These meetings, along with routine interactions at the site, continue to build the trust both parties need to ensure compliance and progress.
Internally, the senior vice president of quality and regulatory leads a weekly review with a cross-business audience, including the executive team, regarding ongoing regulatory inspection activity, regulatory commitments, and customer quality commitments.
In a recent 12-month period, Catalent underwent 52 inspections from 20 global regulatory authorities. It is common to average more than 20 customer audits in a month.On a monthly basis, a deeper review is carried out for quality performance, quality and compliance highlights, and quality initiatives with the executive and business leadership teams. Regulatory inspection outcomes, customer audit outcomes, and global quality/operation initiatives are discussed through global telecoms to ensure that best practices are leveraged across all sites for consistent action.
During these discussions, the management team, including senior-level participants, assesses the root cause of any problem, reviews customer comments and marketplace feedback, and develops ways to improve the local site, the business unit, or Catalent’s global operations.
A formal quality management review, led by the CEO, occurs quarterly and is attended by the executive leadership team, associated functional heads, Catalent business unit vice presidents, site general managers, and site quality leaders.
Annually/quarterly: A management review process, including Catalent’s most senior quality and operations leadership, along with customer representatives, is co-led and includes transparent discussion on current and past scorecard measures. This session generates a collaborative, long-term action plan that is based on continuous-improvement initiatives.
Catalent collaborates with regulatory and industry organizations to achieve industry improvement, establish policies, and effect change. International regulatory agencies have solicited the company’s senior-level representatives to share their expertise and intelligence, as well as advice on policy and industry improvements. Some participate on advisory boards and even play a role in shaping policies.
It is essential for pharma/biotech companies to constantly reassess their QMS strategy, seeking ways to improve. They must also make sure their outsourcing providers are working as trusted partners, equally committed to achieving compliance success. Strategic partnering for excellence involves selecting a highly qualified contractor, developing a clear agreement wherein both parties understand and thrive, and having a process to look to the future.
With a robust and stringent yet flexible strategy, a company can be confident of being inspection-ready at all times and producing safe and effective pharma/biotech products—whether processes are done in house or by a global outsourcing organization. The characteristics of a contract receiver must ensure the contract giver’s success.
Thinking ForwardBoth outsource partners must not only manage the processes in the approved quality agreement but also work with high attention to detail and constant review of systems. This includes a rigorous management of the review process, including an internal audit program that is robust and meets the contract giver’s expectations relative to its auditing program. It should include a strong investigation process with a foundation in root-cause analysis and cGMP investigations of deviations and change orders. If the contract giver has agreed to sub-contract work from its contractors, it is important that the contract receiver has a supplier auditing program that meets the contract giver’s expectations and takes strong stewardship of materials and costs.
A strategy to work within industry organizations, pharmacopeias, and regulatory forums helps to further strengthen the partnership as a relationship. A contract receiver that is working within standards-setting bodies such as pharmacopeias or regulatory review processes is a contract receiver that expects to help provide solutions to its partners, with a thorough understanding of how standards are written and set for the industry. This should mean participation on pharma/biotech association advisory boards and participation in industry working groups or even expert committees or panels within organizations, such as national pharmacopeias. Contract receivers should be actively involved with international industry associations and standards and guidance-setting bodies, including academia, to ensure that they understand current regulatory interpretation and can help influence pharma/biotech directions.