SM Mudda, Chairman, Regulatory Affairs Committee, IDMA, Mumbai examines where India’s pharma industry stands in terms of current expectations of the regulatory authorities and the state of GMP compliance in the sector
Meeting regulatory expectations
Nothing much has changed as far as regulatory expectations are concerned. The focus of inspection, finding how companies reacted when things went wrong or were changing under pressure, remains the same even now. It was expected that the companies would do a detailed investigation of the failures to find the root causes rather than just building arguments for release of the products. The investigations doesn’t seem to have met the required standards, with particular reference to complaints, rejects, deviations and out-of- specification data. No significant changes are seen in this area either.
The emphasis on top management responsibility continues to remain a major expectation from the regulators, as evidenced by the following statements from Dr Janet Woodcock, Director, CDER, US FDA. She states, “Pharma quality management is lacking and we are not anywhere near where we need to be. And it seems as though industry’s objective today is to continue to meet regulatory standards which are minimal expectations, versus adopting a commitment to high-quality medicines. A large number of recent manufacturing failures can be traced to failures in the form of quality management system (QMS). In some cases, the QMS ignored and failed to follow-up on customer complaints. In other cases, multiple repeated deviations were treated as separate incidents, rather than an obvious trend. Another recurring theme has been investigations ‘to nowhere’, concluding with no additional understanding or insight into why the problem may have occurred and thus no hope for prevention. All of these failures suggest a QMS that is insufficiently empowered or resourced to adequately to carry out its essential functions”.
Current state of GMP compliance
Failure in carrying out investigations with an intent to identify the true root cause and lack of management responsibility continue to remain major concerns as seen from the various deficiencies reported and warning letters issued in the last two years. Despite implementation of remedial measures by the companies with assistance from eminent consultants, a resurgence of data integrity and quality issues are plaguing our industry. In 2015 alone, findings from 218 major inspections done by The Medicines and Healthcare Products Regulatory Agency (MHRA) and a significant number of USFDA warning letters have cited data integrity issues, predominately related to the laboratory systems.
A significant concern is that companies which failed inspection initial but were given a clean chit after implementation of CAPAs have found themselves in deeper trouble in subsequent inspections. As if this was not enough, the indirect regulatory actions arising out of the failures of suppliers/ vendors, contract testing laboratories and clinical research organisations (CROs) have aggravated the issue; leading to a sudden and unexpected impact on the business. It appears as though we are not sure of the outcome of the next inspection and our GMP compliance continues to remain consistently inconsistent.
The industry continues to remain at a tipping point. The question that needs to be asked is, “Are doing more of the same because we need to find a quick solution or are we focusing with a learning mindset on something better and different because it is a right thing to do?”
The tipping point
Adopting a good quality, system-based approach for compliance with GMP continues to remain at the top of the industry’s agenda. However, support from the top management for a paradigm shift in its approach towards GMP compliance is yet to be demonstrated in full measure. Whatever has been done in these areas appears to be reactive and inadequate for the challenges we are facing. The power of a quality system as a foundation in creating a sustainable culture of quality has not been fully realised at all levels in the organisation. This has led to a piecemeal and need-based adoption rather than being regarded as the philosophy behind the practices and a key driving force for compliance.
Is pharma quality like an elephant in the dark?
In a recent blog post, Dr Ajaz Hussain, an eminent thought leader in the areas of quality and compliance, with an understanding of both the worlds, India and the West, underscored the importance of adopting a systems-based approach by posing the right question, ‘Is pharma quality like an elephant in the dark?, and has equated it to the story of six blind men touching and describing what they observed in the dark. None of the versions came close to describing the elephant. This is quite similar to our inability to share our observations with others from various functions within the company and finally integrating the information through a well-designed Pharmaceutical Quality System (PQS) to complete the whole picture i.e. to understand the real contributing factors and the root causes that have been identified by the regulators as expressed eloquently by the CDER Director in her statements reproduced above.
A system is the product of interacting parts. Unless a quality systems approach is adopted it is not possible to integrate the activities of all functions. Improving them in isolation will not improve the system.
Deming’s 94/6 Rule
The following quote from W Edward Deming conveys the importance of systems-based approach. He says, “94 per cent of the problems in the business are system-driven and only six per cent are people driven.”
New initiatives from the industry
It is heartening to see that there has been a significant change in the mindset of industry leadership in acknowledging the enormity of the issue involved and initiating preventive measures at individual company level and also at the industry level collectively. There is a clear understanding that the underlying reasons for failures are more behavioural than technical. The challenge now is to create a second level of leadership who can represent the top management’s intent in letter and spirit and convert it into a concrete action plan for implementation.
The individual companies have adopted many technical measures such as automation of systems, control on electronic data and education of the personnel for building the required skills needed to ensure consistent compliance.
Likewise, the industry has started various initiatives to ensure that there is an industry-wide focus and commitment at creating a culture of quality. For example, IPA’s Quality Forum is working on bringing the large companies together to address the issues and to jointly develop solutions. The Quality Forum has been formed with a clear structure and roadmap to help the Indian pharma manufacturers achieve global benchmarks in quality.
There is also increasing focus on developing and using quality metrics for assessing the level of compliance in the industry by identifying meaningful leading and lagging indicators. Quality metrics is going to be an important monitoring tool during the management review of quality.
The issues related to data integrity continue to be a main topic of concern and interest. A data governance system is being implemented at many companies. It is considered as an integral part of the company’s quality system. An organisation-wide awareness is being created to understand the importance of data quality and integrity in patient safety. The industry has recognised that an environment which encourages transparent and fearless reporting of failures is key to maintaining data reliability.
However, misconceptions on issues related to data integrity and breach of data integrity has to be resolved to remove excessive concerns/ fear associated with them. Stan Woollen of US FDA coined the acronym ALCOA that stands for Attributable, Legible, Contemporaneous, Original and Accurate to identify elements of data quality. Non-compliance with any of these data quality
attributes is at times likely to be interpreted as breach of data integrity. Such interpretation without adequate investigation to identify the root cause in failure to meet the requirement of data quality has to be avoided by all. Constant education about the differences and proactive transparent engagement with all employees and regulatory agencies will help resolve the misconceptions.
Another key issue that requires immediate attention is education of the employees at various levels. This need has been identified from the findings of various surveys and several activities are being initiated by the industry in this direction.
Investment in education – Need of the hour
A survey conducted by management consulting firm Ernst & Young identified lack of education and emphasis on quantity over quality as key root causes of data integrity issues. Often, employees were not educated or trained to understand GMPs. This caused employees to consider activities as a chore rather than understanding their relevance in light of GMP.
Another survey, ‘Managing Growth Through Better Compliance Management,’ got responses from 33 pharma groups in the country where more than 64 per cent said that lack of skilled people to manage compliance was a key drawback. The survey found that 55 per cent of those responding believed their compliance teams were not sufficiently trained.
“There is an urgent need for more effective training, coaching and mentoring – to remove fear and empower the employees,” states Dr Ajaz Hussain, Executive Director, NIPTE, US in one of his articles.
The need for education of the personnel has emerged as one of the important corrective and preventive measures to maintain a state of compliance. Education, thus is being considered as a strategic investment to prevent non-conformance. Any cost incurred for compliance through preventive measures will eventually save the cost of internal and external failures. It follows a ratio of 1:10:100 thus proving it as a wise investment.
IDMA’s initiative
Indian Drug Manufacturers’ Association (IDMA) has introduced several education initiatives realising the need to strengthen the capabilities of the personnel. The Department of Pharmaceutical (DoP), Ministry of Chemicals & Fertilisers has initiated a nation-wide GMP training programme in partnership with IDMA for helping the SMEs to voluntarily upgrade the GMP standards to the current global standards. The programme titled, ‘GMP workshop for SMEs – Schedule M & beyond’ has been designed by IDMA and DoP and so far workshops have been conducted successfully in six different cities. Similarly, a new training programme called, ‘Meeting Quality Challenges & Achieving Global Compliance’ has been jointly planned by DOP and IDMA in the current year and will be conducted in four cities in India.
IDMA has also realised the need for training industry professionals with a specific focus in modern PQS since they are at the forefront in representing the management’s quality intent from inspection to resolution of deficiencies and implementation of corrective and preventive action (CAPAs). In the wake of ever increasing regulatory bar, expectations from quality assurance (QA) professionals for demonstrating an ongoing compliance with GMPs have increased. Lack of formal education of our QA professionals in concepts of quality management is found be one of the key areas that requires an immediate remedial measures.
IDMA has planned to collaborate with leading UK-based GMP consultancy and education firm NSF Health Sciences (formerly known as David Begg Associates-DBA), leaders in pharma quality and technical education and pioneers in quality management and culture building to provide a formal education in best-in-class PQS to the industry professionals to help them deal with the current expectations.
An Advanced Executive Course in Pharmaceutical Quality Management System (PQM) has been designed on the framework of Qualified Person (QP) training course by NSF and IDMA. The course includes practical modules and case studies built on current focus areas as a part of the training to get hands-on experience. Pre – eminent trainers with specialist experience, including ex- MHRA inspectors who provide the training for QPs in the UK with an unsurpassed success rate of 98 per cent will provide the education in India. The course is designed for a duration of 10 months with an examination to certify successful participants.
While the certificate in PQM will provide formal recognition to an individual for demonstrating proficiency in PQS, it will also help the company to protect its reputation as a supplier of quality medicines and earn regulators’ trust and respect. Besides, greater efficiency will lead to improved profit margins. It will create an environment in the company that will attract and retain the best people.
This initiative of IDMA is a plan for providing concrete long term education programme that will build the strength of quality professionals across the industry with a formal certificate of international standards and an ability to match global professionals.
Deming’s 14 principles and obstacles for transformation
While all the above initiatives are laudable, we need to understand that most of these have been reactive measures adopted in the face of challenges encountered in the last few years. While they have been benefiting the industry to ensure sustainability of these initiatives and consolidate the benefits, the industry is required to go through a transformation before it adopts proactive measures successfully. The lessons from Deming’s book ‘Out of the Crisis’ show us the way forward.
While it is realised and accepted that top management engagement and support is necessary, Deming states, “It is not enough that the top managements commit themselves for life to quality and productivity but they must know what they are committed to – that is, what they must do”. Quite often the management support is demonstrated by instituting a quality program that is ceremonial in nature. The actions can’t be in the nature of ceremonial support but have to be concrete. The following statement from his book emphasises the importance of actions. “A quality programme for a community, launched by ceremonies with a speech by the governor, raising of flags, beating drum, badges, all with heavy applause, is a delusion and a snare.”
Such programmes can give an impression of progress being made but in reality unless supported by concrete actions the benefits will elude us. It is therefore necessary to learn from teachings of Deming and follow his 14 principles for management of quality to overcome the following obstacles that stand in the way transformation:
- Lack of constancy of purpose
- Emphasis on short – term profits: Profits follow good products. Short-term thinking – the opposite of constancy of purpose – in order to stay in business may lead to cutting of expenses related to long term goals such as: training, quality assurance management, maintenance, etc.
- Performance – based evaluation: It nourishes short term performance, stops long term planning, builds fear (management by fear), destroys teamwork, nourishes rivalry and politics. The effect is exactly the opposite of what it promises. It has to be acknowledged that apparent difference between people arise almost entirely from action of the system that they work in, not from the people themselves. Modern principles of leadership should replace the annual performance review and therefore the first step in the company should be to provide education in leadership. More careful selection of people in the first place, better training and education after selection will be the way forward. A leader instead of being a judge, will be a colleague; counselling and leading his people on a day-to-day basis, learning from them and with them. The performance- based evaluation was identified as one of the potential problems by Dr Ajaz Hussain in his interaction with the industry and he has stated in his article, “There is a tendency to incentivise outcome rather than the process of getting the outcome and that is the potential problem”
Conclusion
It has often been said that ‘Quality is too important to be left to the quality controllers alone’. The significance of the statement is realised in the present circumstances where focus on the management aspects of quality rather than adherence to inspection-oriented practices is of paramount importance to remain in state of quality and regulatory compliance. The focus thus has to be on making quality as a primary objective of the company and all efforts should be on single-mindedly achieving this objective by overcoming the obstacles discussed above that stand in the way of transformation. The significant learning from Deming’s teaching that quantity driven key performance indicators (KPIs) have to be replaced with key behavioural indicators (KBIs) to build a strong leadership for quality in the organisation has to be put in practice.
The realisation that adoption of PQS and risk-based approach is vital to the success of the business has to be percolated down to all levels in the organisation. This new learning coupled with a focus on implementation of the following initiatives will help regain the trust of the customers and the regulators alike.
- Development of second level leadership through on-going education initiatives
- Creating an environment of fearless reporting of failures
- Objective, independent retrospective investigations of the failures to identify the actual underlying technical and behavioural contributing factors, impact assessment of the findings on the quality of products and implementation of appropriate CAPAs
- Transparent documentation and reporting of the findings to the regulatory agencies
- Creating a governance system for ensuring reliability of data (Data Integrity) and
- Introduction of a robust and meaningful quality metrics that provides information of lagging and leading indicators for management review of quality.
This approach has paid good dividends to some of the major companies who have been able to come out of crisis. If this model is followed by other companies, which certainly is happening, we can take real pride in our being a Pharmacy to the World.
References:
1. Out of the Crisis – By W.E.Deming
2. Ajaz’s Insights on Pharmaceutical Technology Education, Training and Experience for the 21st Century
3. Pharmaceutical Quality: Elephant in the Dark or Six Blind Men – By Dr.Ajaz Hussain, Founder, Insight, Advice & Solutions, USA and President NIPTE, USA.
4. Data Integrity Survey- By Ernst & Young
5. Managing growth through better compliance management – By Delloite
6. Articles and Presentations – By Mr. Martin Lush, President, NSF Health Sciences, UK.