Principles and Practice of Pharmaceutical Medicine

which are relevant to public health protection in

Third World countries.

MA holder’s responsibilities:

To have a qualified person responsible for phar-
macovigilance.

Establishment and maintenance of a system

for collection, evaluation and collation of all

suspected adverse reaction information so that

it may be accessed at a single point in the

community.

Preparation of six monthly scientific reports and

records of all suspected serious adverse reac-

tions for the first two years after marketing,

annual reports for the next three years and there-

after at renewal of the authorization.

Reporting to the member state concerned within

15 days of receipt information on all suspe-

cted serious adverse reactions within the

community.

Reporting to member states and the Agency

within 15 days of all suspected serious unex-

pected adverse reactions occurring in Third

World countries.

GMP

Manufacturers’ licenses were issued by the UK

Licensing Authority from the inception of the

Medicines Act to cover all manufacturing opera-

tions, including those previously embraced by the

TSA. The Medicines Inspectorate laid down stan-

dards in itsGuide to Good Manufacturing Prac-

tice, otherwise known as ‘The Orange Guide’; the

most recent edition was issued in 1997. Although

the issue of manufacturers’ licenses remains a

national regulatory function, it is governed by the

standards set in EC Commission Directive 91/356

EEC, which can be summarized as follows.

The Directive lays down the principles and

guidelines of GMP to be followed in the production

of medicines, and requirements to ensure that man-

ufacturers and member states adhere to its provi-

sions. Manufacturers must ensure that production

occurs in accordance with GMP and the manufac-

turing authorization. Imports from non-EC coun-

tries must have been produced to standards at least

equivalent to thosein theEC, and theimportermust

ensure this. All manufacturing processes should

be consistent with information provided in the

Table 33.3 Annual input of adverse reaction reports
to CSM and total number of fatal reports

Fatal reaction as a
Total ADR Total percentage of total
Year reports deaths ADR reports

1964 415 86 5.9
1965 3987 169 4.2
1966 2386 152 6.4
1967 3503 198 5.7
1968 3486 213 6.1
1969 4306 271 6.3
1970 3563 196 5.5
1971 2851 203 7.1
1972 3638 211 5.8
1973 3619 224 6.2
1974 4815 275 5.7
1975 5052 250 4.9
1976 6490 236 2.6
1977 11 255 352 3.1
1978 11 873 396 3.3
1979 10 881 286 2.6
1980 10 179 287 2.9
1981 12 357 303 2.5
1982 14 701 340 2.3
1983 12 689 409 3.2
1984 12 163 340 2.8
1985 12 652 348 2.8
1986 15 527 403 2.6
1987 16 431 390 2.4
1988 19 022 410 2.2
1989 19 246 475 2.5
1990 18 084 377 2.1
1991 20 272 541 2.7
1992 20 155 478 2.4
1993 18 066 480 2.7
1994 17 546 412 2.3
1995 17 668 467 2.6
1996 17 191 393 2.3
1997 16 637 455 2.7
1998 18 062 529 2.9
1999 18 505 560 3.0
2000 33 094 610 1.8

430 CH33 THE DEVELOPMENT OF HUMAN MEDICINES CONTROL IN EUROPE