In part 1 we heard a little about what are some manufacturing standards. We learn't that to produce the final batch of iPPS it's not just a slapping together of a few ingredients adding a pinch of sulphur and bringing everything to the boil and viola.
Part 2 will now explore a bit more about what is GMP and just what the FDA demands of us...well of Bene..
Let's check out the points we are covering:
FDA - GMP
GMP simply stands for Good Manufacturing Practice. Think of it as a guide and a manual for best practice in terms of what the FDA looks for and what is indeed randomly audited once it's all set up. Now the manufacture of a drug has to live up to certain standards, specially if they are to be given the golden keys to one of the biggest Pharmacy markets on earth, the USA.Let's now take a sneak peek of some typical things the FDA look for and how much detail they go into.
AN EXAMPLE OF DETAIL
Just take a look at the following as just a snapshot of the diligence and umpteenth level of quality that's demanded by the FDA.I'll take just a few broad headings and delve down into a little selected detail but for a comprehensive look for yourself, take a flick at Reference 1 in the reference section at the end of this post below.
PERSONNEL
There should be adequate no. of people adequately trained to handle the drugs that are being manufactured, this includes all types of training and records thereof.
PERSONAL HYGIENE
Even there are a number of points under this category. Clean clothing and good sanitisation are just a couple of the many points mentioned.
BUILDING AND FACILITIES
The FDA goes to great length to specify so many factors here, from the air conditions (right temp, humidity for manufacture) to adequate storage and maintaining records of the same, they mention lighting requirements and even separation of lab areas from production areas. Onus is on the manufacturer to ensure adequate provision of showering and maintaining of staff cleanliness as part of the process.
UTILITIES
Perhaps something out of one of the movies but the FDA talk about Pressure locks, air filtration systems and the minimisation/elimination of chance of cross contamination. I myself have heard of very elaborate and modern facilities over at the Bene manufacturing plant.
Hmm Airlocks gets a mention, hey I've never been to Bene (sorry) but it's possible at least a few of their rooms are fully dust proof and have these air lock type devices?
Even the pipework gets a mention.
Ok here is a shortened version of some of the major topics in the guidelines:
WATER CONTAINMENT
LIGHTING SEWAGE and REFUSE PROCESS EQUIPMENT
MAINTENANCE AND CLEANING
CALIBRATION
COMPUTERISED SYSTEMS
DOCUMENTATION RECORDS
USE RECORDS OF MACHINERY
RECORDS OF RAW MATERIALS
MASTER PRODUCTION CONTROLS AND RECORDS
BATCH PROCESSES
Mozz's Notes: I personally again have heard this is a very onerous step, accurate and precise recording of batches are to be maintained particularly in transport across to other countries not unlike the batches that were sent to Aus and US for their SAS and EPA programs, this takes time and adequate audit trails must exist to facilitate in tracking and conforming to the high standards the FDA imposes. I heard it could've been one of the reasons some of the SAS patients were delayed in accounting for such batches.
QUARANTINE SAMPLING TESTING
STORAGE PRODUCTION AND IN-PROCESS CONTROLS
CONTAMINATION CONTROL
Mozz's notes: It's not just about, the successful production, the FDA gives guidelines for what to do with waste and how to handle it, it all needs to be documented and receipted. "Records should be maintained for each shipment of labels and packaging materials showing receipt, examination, or testing, and whether accepted or rejected." 1
LABEL ISSUE AND CONTROL
PACKAGING
OPS STORAGE
WAREHOUSING AND DISTRIBUTION GUIDELINES
LAB CONTROLS
STABILITY MONITORING
VALIDATION POLICIES
QUALIFICATION PROCESSES PROCESS
VALIDATION CHANGE CONTROL
COMPLAINT HANDLING
RECALL HANDLING
Paradigmers, all the topics in CAPITALS above have their own subsections! The more you read, the more you understand the scale and the detail required. This really isn't a backyard fly by the night process. The barrier to entry is huge...No one is going to be able to easily set up shop, mimic our precise molecular structure down to the moiety level and set up just a precise manufacturing and complying facility. If they get through that they still have to show an exact match and even then they breach various patents. This is one true area we got licked.FDA are happyso much so that they implore us to ONLY use the Bene batches for any of the upcoming trials. This really is a vote of confidence in our business partner and bodes well for us as shareholders.
A MANUFACTURING FORECAST
Right, another Mozz © chart to digest, this one depicts possible number of overlapped indicational patients that elect to take our drug. Yes quite conservative and please don't forget you need to multiply the below numbers by 12 because each patient undergoes 12 injections right? (except for MPS which is even more, ie one a week!). Gee the numbers add up...Bene are going to be rather busy. But, fear not, this projection plan will already be on their table...I am sure of the discussions that PAR have had with Bene already:
Total Number of vials to be manufactured:
CONCLUSION
Par-Peoples, manufacturing in Germany is of a high standard generally. Their attention to detail their pride in workmanship and their rich culture of getting it right is simply a boon for us. Add this level of manufacturing to the high standards demanded by the FDA and do this for decades and it becomes clearer as to who exactly our business partner is and what they are capable of! Our eyes have been opened just a fraction more in reading the detail. But as per usually, please do not rely on just me and what I bring to the HC Par Table. I encourage you to research on your own. Take a look at reference (1) below and spend just 5 minutes flipping through the mountains of points that one must cover to be bestowed with the award of GMP along with those random FDA audits!
My rationale for this post was two fold, one to post about the high standards of manufacturing and the great relationship we have with one of the best, Bene. The other reason was simply to give you taste of the amazing detail the FDA demands of such manufacturers when dealing with pharmaceuticals and what must be achieved before one is allowed to sell into the US. No wonder so many other countries basically look to the FDA.I spend time to put a high level timetable together, but can you just imagine some of the detail the folk at PAR and Bene must deal with? And to think it's not just one indication they are dealing with, it is several in multiple markets. It will be a real achievement once we are given the final go-ahead, a day of celebration an yes, even a multiple rock*t pics scattered randomly through the HC catacombes.
But finally,
Viel Glück an alle Inhaber
(Good luck to all holders)
DISCLAIMERS
Yes yes we know to do our own research Mozz...bleedingly obvious. But remember, there are risks. I mean there are risks in anything we do...going outside...staying indoors...even exercising can be risky, not eating well...I don't need to go on.My point is that you still need to assess it for yourself. Despite all the experts, all the research, all the forecasts and the experience and history we have had in our lives, things can still go wrong. Never invest 100% into the one product, the one class. Just like a quality car from Germany, the Benz (E400 would be my drive of choice)... or the Porsche Turbo..even the lovely Audi R8.. iPPS is one decently made product. Spread your bets! Not unlike my 12 year old dishwasher, this particular German product is one to back. My views!
REFERENCES1]
https://www.fda.gov/media/71518/download
(20min delay)