1. INTRODUCTION
Last modifications on European GMP, which are taking effect on Mach 15th, (Chapter 3 and especially Chapter 5) are going to impact on existing facilities and equipment, and they are going to force a rethinking of all steps and measures to be taken in order to avoid cross contamination; not just for these products so-called “high potency” but in general for all pharmaceutical products. Every pharmaceutical product must have a risk analysis based on a toxicological assessment. Measures to be taken in order to avoid cross contamination will be determined in accordance with a risk analysis, based on the Quality Risk Management principles and they should be commensurate with the risks
2. THE OLD LACK OF DEFINITION: “GET READY FOR THE WORST”
On previous versions of Chapter 3 and 5 dedicated facilities and containment measures were recommended for “certain hormones, certain antibiotics, certain cytotoxics….”but there was no further information about which hormones, antibiotics or cytotixics could be considered among these “certains” That lack of definition give rise to two kind of facilities: High containment facilities and standard facilities. When in doubt about the categorization of a product this was branded as “High Potency “and it was processed in dedicated facilities or high containment facilities with all those measures for high containment: Once through air systems, Bag In/Bag out filters, closed process, PPE for autonomous breathing, decontamination showers… The advice was: “In doubt get ready for the worst” but it meant expensive facilities and high energy costs.
3. THE NEW APROACH: “EVERY PICTURE TELLS A STORY”.
With the new GMP approach a risk analysis based on the Quality Risk Management principles is mandatory for any medicinal product and the analysis must include a toxicological evaluation for every case, not just for “certain hormones, certain antibiotics, certain cytotoxics….” This risk analysis should be used to assess and control the cross-contamination risks presented by the products manufactured and measures to be taken should be commensurate with the risks. Thus there are no longer two options: high containment or standard manufacture; from now on there will be as may options as risk degrees and specific containment or protection measures should be defined for each case .
4. STRESS TEST NOT JUST FOR BANKS
Risk analysis and toxicological evaluations are going to be a real “stress test” that will bring up lacks and deficiencies in some current facilities which should be adapted to the new regulations; but on the other hand, all of these facilities which manage to fulfill the new regulations will have a wide open door to manufacturing these products which were considered just in the border of “High Potecncy” and, in accordance to the old saying of getting ready for the worst, they required high energy cost and expensive facilities and equipment. Now, with a correct application of the regulations it will be possible to manufacture “certain” medicinal products in facilities with reasonable operating costs.
5. THE CLOCK IS TICKING
New changes in GMP will become effective in March 1st 2015. There will be a leeway of some months for risk analysis and toxicological evaluation in order to categorize the products in current manufacturing or to be manufactured. June 2015 for new products to be manufactured in a multiproduct facility, and December 2015 for products under current manufacturing. The critical point will be to use risk analysis and toxicological evaluation checking if facilities and equipment are adequate to avoid cross contamination.
6. CONCLUSION
There are medicinal products, and there will be more and more, which will require dedicated and high containment facilities, more and more complex and sophisticated; but at the same time there are a wide range of products located just under the concept of “High Potency” which, in the light of the new approach on Chapter 3 and 5, will require measures for control contamination and containment commensurate with the risk, both at technical and operating levels. In this way small or moderate refurbishment of the facilities could open up new opportunities of manufacturing with competitive operating costs compared with these on the classic dedicated or high containment facilities.
Miguel Ruiz
mruiz@ingelyt.com
En INGELYT estamos a la vanguardia y somos pioneros en el sector en cumplir con el Diseño, Implantación y Mantenimiento de Planes y Programas de Prevención y Gestion de Riesgos Legales y Penales (CORPORATE COMPLIANCE)