Volume 7: Medicines and Cosmetics
2. The operation of medicines licensing
Evaluation of the arrangements for the control of medicines
Human medicines: Evans-Cunliffe Report
Veterinary medicines: Cunliffe Report

2.75 There was concern during 1987 that Medicines Division was showing signs of overload, and Ministers asked Dr N J B Evans and Mr P W Cunliffe to study the arrangements for the control of human medicines in the UK. The Minister of Agriculture, Fisheries and Food then asked Mr Cunliffe to conduct a parallel review of the licensing and control of animal medicines within MAFF. These reports highlighted significant defects in the handling of medicines licensing and were the catalyst for substantial organisational changes.

Human medicines: Evans-Cunliffe Report

2.76 In December 1987 Dr Evans and Mr Cunliffe produced their Study of Control of Medicines ('the Evans-Cunliffe Report'). ¹ Their terms of reference were:

To examine the issues for DHSS arising from the continued increases in licence applications and other work under the Medicines Act and to recommend ways of dealing expeditiously with this work, while maintaining adequate standards for the safety, efficacy and quality of human medicines in the United Kingdom. ²

2.77 The Evans-Cunliffe Report stated that the basic framework of medicines control in the UK was satisfactory:

The Medicines Act 1968 has stood the test of time well, as has the general principle whereby a licensing office takes advice from independent expert bodies and reports to Ministers. The high reputation which the UK deservedly holds for medicines control depends upon the excellence of the professional judgements made by staff and those advisory bodies, on the balance of benefit and risk from medicines. ³

2.78 The professional and expert judgements made by staff and advisers received praise:

. . . [W]e are satisfied that the judgemental decisions are generally soundly made. All the evidence, and our own experience and observation, indicate that the quality of the professional and expert judgements made by Medicines Division staff and by the members of the expert advisory committees is very high. This expert competence is in fact the great strength of the UK system, and when recommending change in the present arrangements we have been especially concerned not to weaken its excellence, which has served the public well. ⁴

2.79 The Committee systems were also reported to be working well:

We examined the work of all the Section 4 Committees (except the Veterinary Products Committee, which lay outside our terms of reference) and their subcommittees, and judge them to be well-run and highly expert bodies. Their chairmen and members carry considerable responsibility and a heavy burden of paper-work in preparation for meetings, and the country is much indebted to them for their labours. ⁵

2.80 The Report concluded, however, that there were problems within Medicines Division that needed to be addressed. They identified in particular:

1. delays;
2. minor documentary errors;
3. difficulty in recruiting and retaining professional staff;
4. antediluvian computer support;
5. problems with the paper filing system; and
6. complex organisational structure preventing effective management. ⁶

They concluded that overall the Division was unduly constrained from without and lacked resilience within. ⁷

Overload and delay

2.81 The Evans-Cunliffe Report discussed problems of overload within the Division and resultant delay, stating, 'delays and errors are classic indicators of overload'. ⁸

The workload from licence applications received by Medicines Division of DHSS has gone up steadily and is still rising. On the whole, the office has coped surprisingly well with this increase and without proportionate increase in staff, but it is now showing signs of overload. Licences for New Active Substances (ie, the important new drugs) are currently held up on average for as much as two years, compared with the European Community (EC) specified figure of 210 days, and many minor applications are held up almost as long, compared with the EC figure of 120 days. ⁹

And later:

There are . . . sometimes substantial delays in reaching the decisions - delays which are in part attributable to shortage of professional staff though they may also in part reflect the lack of effective management. ¹⁰

Recruitment and retention of professional staff

2.82 Problems in recruiting and retaining pharmaceutical and medical experts were described as follows:

The other principal area of difficulty relates to staff: because civil service salaries for pharmacists and doctors are uncompetitive and there is too little secretarial and other support, it is difficult to recruit experienced professional staff for this highly specialised work and - once trained and experienced - they leave for posts in industry. Other rigidities compound the problem, for example the control of staff by arbitrary head count, and the dilatory procedures for filling vacancies. ¹¹

2.83 This view was echoed in evidence heard by the Inquiry. Dr Gerald Jones stated:

There was, unfortunately, a considerable turnover of staff. We were recruiting almost permanently. The board recruiting doctors from outside, I called it virtually a standing committee; it had to meet - which I served on - virtually every 3 months. As soon as you were able to appoint a doctor you found that someone had moved on within the Department. The Division stood at about 20 or 25 doctors at that time. ¹²

2.84 Dr Jefferys also commented on staffing levels in Medicines Division:

At that stage [1988], there were only 5 physicians in MB3A, one of whom was working full time on the Opren litigation. For most of this period we were actively recruiting for a sixth physician. In addition, there were 3 toxicologists in the group. However, for much of this period only one toxicologist was working full time because both the other toxicologists were on extended maternity leave.

By contrast, there are now 27 medical assessors, 8 toxicologists and 4 statisticians in the Licensing Division and 26 physicians in the Post-Licensing Division (including Pharmacovigilance activities). In total there are now approximately 550 staff within the Medicines Control Agency. In 1988 the figure was closer to 220. ¹³

2.85 He added:

These resource difficulties inevitably had implications for the work of the Division. For example, in 1988, renewals of product licences were handled purely administratively without input from physicians because of the staff shortages. In addition, the processing of abridged licence applications was subject to a two year backlog. By summer 1989 the position had started to improve in that the number of physicians within MB3A had increased to 7 and the work on the Opren litigation [which had occupied considerable resources] had decreased, but the major improvement only occurred in the early 1990s with the full establishment of the MCA. ¹⁴

2.86 More generally on staff structure the Evans-Cunliffe Report commented:

. . . the staff are structured in separate hierarchies representing the professional disciplines making up the workforce - in this case hierarchies of administrators, doctors and pharmacists respectively. As the structure and subdivisions of the different hierarchies differ from each other, with no common relationship to the several 'businesses' into which the work of the Division can be divided, it is difficult to design simple operational policies and almost impossible to engender any feeling that staff are working together to a common purpose. ¹⁵

Computing and information technology

2.87 The Evans-Cunliffe Report also found that computing and information technology support within the Division was seriously deficient, and that the database used for the processing of applications and the supporting data was almost unusable because it was erroneous and out of date:

There is an urgent need for more and better computerisation of the office processes relating to licence applications, and to the monitoring of adverse drug reactions. ¹⁶

2.88 Dr Purves, Senior Principal Pharmaceutical Officer, gave the following explanation of the computerised database and its limitations:

The Norsk product licence database used by Medicines Division in 1988 stored information on all product licences and CTC's. This database recorded information on all active ingredients in products. It did not, however, record whether bovine materials were used as excipients (any other ingredient used in a product i.e. to stabilise the active ingredient) or as ingredients or reagents. (NOTE: - an ingredient ¹⁷ is a material used in the manufacture of products, which is removed during purification and is not present in the finished product). The most effective way of getting up to date and complete information on which bovine materials were being used in medicines was to consult the manufacturing industry. Getting this information direct from the manufacturers was particularly important because the source of the bovine material was crucial. In some cases only the manufacturing company would have the details of who their suppliers were and from which country their raw materials were derived. ¹⁸

The paper files

2.89 As a consequence of the computing problems there was heavy reliance on labour-intensive clerical operations and on traditional paper files, called 'gold files'. However, there was no effective system for keeping track of the files or of the transit of work through the office. The Report stated:

The thousands of current and previous licence applications are moved around the office in cardboard folders, the so-called gold files. It is astonishing that there is no reliable way of finding files within the building. Some months ago, DHSS introduced a file tracking system in which staff read-off bar codes into a central computer, but it is not yet comprehensive nor fully operational. File-tracking is an essential tool not only for finding and linking files but also for monitoring the transit of work through the organisation. We RECOMMEND that a high priority be given to completing and developing the file-tracking system. ¹⁹

2.90 Clearly the response of Medicines Division to the potential dangers associated with BSE would involve, at some point, establishing the extent to which bovine products were included in medicinal products. Given that applications for product licences involved the submission of detailed data relating to the active ingredients and processes used in the manufacture of particular products, considerable information should have been available to administrators. However, as highlighted by the Evans-Cunliffe Report, neither the computer system nor the paper files were adequate for this purpose.

Structural/organisational difficulties

2.91 Furthermore, the Evans-Cunliffe Report stated that aspects of the running of the Medicines Division indicated a lack of effective oversight of the Division's work. ²⁰ The Report stated:

Our scrutiny of Medicines Division showed that it is indeed overloaded and will require more resources - some more staff, and computing equipment. ²¹

2.92 The Report also commented adversely on the organisational structure of the Division, which, it stated:

reflects its historic origins as a headquarters policy division and is inappropriate for the present task; in particular the diffusion of managerial responsibility means that there is no effective overall control of the flow of work, and it is frustratingly hard to bring about change. ²²

2.93 The Report recommended alterations in the structure and administration of the Division, but fell short of recommending independent status:

We considered carefully whether the Medicines Directorate should be transferred from the DHSS, as has been suggested, into a Special Health Authority or other independent body, but we decided that the balance of advantage lies in keeping the Directorate within DHSS under special financial and managerial arrangements to promote a considerable degree of autonomy and flexibility, for example over pay for specialised posts. ²³

Veterinary medicines: Cunliffe Report

2.94 Shortly after the publication of the Evans-Cunliffe Report on the licensing arrangements for human medicines, Mr Cunliffe produced his report entitled Review of Animal Medicines Licensing. ²⁴ In summary the report emphasised that there was 'little criticism of the general concept and indeed of the correctness of decisions but considerable criticism of the operation of the system'. ²⁵ Mr Cunliffe noted:

Running through many of the discussions, I detected a feeling that animal health was considered to be a smaller, poor relation of human health. It came through from the industry, from professionals in MAFF and from some members of the [VPC]: in support of this, I was told that the industry was smaller and less profitable, that its professionals in the Civil Service are of a lower grading and that in product assessment, human fears would dominate animal health. ²⁶

2.95 In terms of the staffing difficulties and the pressures of workload, the Cunliffe Report's findings were similar to, though less acute than, those on the human medicines side. It stated:

The present members of the licensing operation have been able to cope with the workload, although at the expense of other activities. Strains are, however, evident and delays are increasing. It is unlikely the present numbers will be able to cope with the future workload unless systems are developed to reduce that workload.

. . .

The problem with professional staffing detracts from the licensing operation. The causes appear to be: -

a) restraint on staff numbers eg Treasury head count

b) difficulty in recruiting because of -

• unpopularity of the Civil Service to professionals
• salaries too low relative to the market
• protracted procedures for advertising and filling vacancies via the Civil Service Commission
• licensing work is highly specialised and hence unattractive in career terms to MAFF veterinary staff.

c) dissatisfaction of those in post because of -

• uncompetitive salaries
• inadequate secretarial etc support
• frustration at the inability to bring about change
• lack of career opportunities within the unit. ²⁷

2.96 The Report concluded:

The UK approach to the control of medicines appears sound and the intellectual and judgmental qualities stand high. Operation of procedures falls short of effectiveness and would be further adversely affected by the future work load. Computing support is disastrously weak and the whole operation is under-resourced and ineffectively managed. External (ie outside the licensing operation) constraints have prevented any attempts at improvement. ²⁸

2.97 The Report recommended improvements in technology; simplification of procedures and removal of unnecessary work; better communications between applicants and the licensing operation; improvements in staffing and personnel; and improved organisational structures. ²⁹

2.98 These chronic shortcomings in so many aspects of the arrangements for control of medicines in the UK were identified at the very time when the Licensing Authorities were called upon to deal with the emergence of BSE. Problems with the database and computing support, with the paper files and their management, overwork, ineffective management and complex structures each played a part in shaping the response, as we explain in the following chapters.

2.99 Some of these difficulties were addressed by the establishment of the Medicines Control Agency (MCA), and the Veterinary Medicines Directorate (VMD), as described below.