Scott Karolchyk, John Scott Karolchyk, MS, RPh, RPh, FIACP 3399 Woodlawn terrace terrace 07849 Lake Hopatcong, Hopatcong, NJ 07849 Key-Whitman Key-Whitman Surgery (Guardian) Center/Guardian Health Health Systems Systems (Guardian) Surgery Center/Guardian May 1, 2017 May1,2017 I. Background and and Expertise Expertise 33 years years of II am aa formulation developer and compounding pharmacist with 33 pharmacist with of experience with high risk sterile and non—sterile experience with high risk sterile non-sterile compounding, formulation compounding, formulation standards, procedures development consulting consulting and USP/FDA standards, regulations. I am aa procedures and and regulations. past President of 0f the International past International Academy 0f of Compounding Pharmacists Pharmacists (IACP) (IACP) of IACP. My resume is is attached and aa Fellow ofiACP. attached for for review. review. I thc true true triamcinolone acetonide/moxifloxacin HCl injectable II developed the triamcinolone acetonide/moxifloxacin injectable formulation formulation Jeffrey Liegner, created and patented Liegnsr, MD. We created along with Jeffrey patented the with the formulation formulation with Imprimis in the testing Imprimis Pharmaceuticals in in 2013. I have been intimately involved in intimately involved the testing and and the formulation and am familiar with its research into development of the familiar with its components, components, research into the development and its its pharmaceutical the pharmaceutical parameters. parameters. I Iowa My educational background includes graduate graduate school school at at the the University University of 0f Iowa 0f Pharmacy where my graduate research research involved College ofPharmacy involved drug drug formulation, formulation, 0f sterile micellar catalysis and compounding of sterile admixtures. catalysis and admixtures. H. II. 2017 by Dr. Jeffery 3 would IIwas was contacted contacted on March 31, Liegner and Jeffery Liegner and asked by Dr. asked ifl if would speak speak with potential retinal Jeffrey Whitman, MD about potential retinal toxicity with Jeffrey associated with toxicity associated with another another version of injection compounded formulation, by pharmacy, Guardian, version of my injection formulation, another pharmacy, by another Guardian, the Key-Whitman Kcy-Whitman Surgery Center, which caused Surgery Center, of visual visual acuity used by caused severe severe loss by the loss 0f acuity in multiple patients. patients. in multiple l , I to be a Kcy-Whitman Surgery II agreed to a consultant for for Key-Whitman Center because Surgery Center because of of my intimate intimate knowledge of this formulation. The scope of the this formulation. the consultation evaluate the consultation was to to evaluate the test them and received formulations from Guardian, test provide professional and provide professional comments. comments. III. Ill. the next fcw weeks I consulted, consulted, in in nonspecific nonspecific terms Over the next few terms with with colleagues collcagues who were were co—inventors of 0f the the original original and true true injection injection and co-inventors and Imprimis Imprimis Pharmaceuticals. Pharmaceuticals. II updated into mechanisms of retinal retinal toxicity updated research research into toxicity and adverse adverse reactions reactions with with Guardian’s and formulations reviewed the Guardian's formulations reviewed the documents sent sent to to me from from Key-Whitman Key—Whitman Guardian’s formulations, Center, which included Surgery Center, included Guardian's and formulations, emails emails from from Guardian Guardian and Key~Whitman testing results KeyWhitman Surgery these results from DynaLabs. Surgery Center and testing DynaLabs. All All these documents are arc attached. attached. II learned that Guardian learned that Guardian consulted with thc the Professional consulted with Professional I Plaintiffs' Notice of Filing Expert Reports - Page 27 of 70 0f America (PCCA) for Compounding Centers Centers of this demonstrably for assistance assistance with with this demonstrably difficult formulation. difficult formulation. Email is attached is attached IV. testing plan which included included testing testing the viscosity of vials II formulated a testing the pH and and viscosity 0f the the vials sent t0 me from Key-Whitman Surgery Center, sent to from Surgery lots. II Center, 6 6 vials vials total total from from two two different different lots. testing results results from DynaLabs and noted n0 testing was reviewed thc the testing and noted no pH testing was completed. completed. V. Pharmaceuticals, confirming II consulted with Imprimis Pharmaceuticals, confirming their manufacturing process process their manufacturing original patented and true, patented formulation. true, original formulation. VI. VI. pharmaceutical cetiainty IIconclude conclude with aa reasonably reasonably degree of pharmaceutical celtainty that that the the formulations formulations are incorrectly not similar from Guardian are incorrectly formulated and and are are not in any any way way to the tested, tested, similar in t0 thc patented formulation of 0f Imprimis Pharmaceuticals Pharmaceuticals and an patented formulation and were were compounded compounded in in an unsafe in both unsafe manner in both formulation process. formulation and process. VII. VII. The formulation formulation proposed and utilized as the utilized by by Guardian Guardian is is not not the the same same as the one one patented and used by Imprimis Pharmaceuticals. Pharmaceuticals. by Imprimis 5~10 times concentration of ofpoloxamer is 5-10 times higher Imprimis’ true higher than The concentration poloxamer is true formulation formulation than Imprimis' three items Specifications (OOS) There were three items Out of Specifications based on on in the the preparation preparation based (OOS) in samples tested tested by (pH). their procedures procedures (pH). by DynaLabs and by by their The formulation formulation pH (7.5-8.0) too high for (7.5—8.0) was too for ocular ocular safety, Imprimis’ pH is whereas Imprimis' safety, whereas is 6-6.5. In ln addition, the pH was OOS because addition, the the tested 6-6.5. because the tested pH was found be 6.6 (lot p11 was found to to be 6.6 (lot 7.2 (lot 53342.42). These OOS lead lead to process errors errors 53718.42) and 7.2 to the (lot 53342.42). the question question of ofprocess Guardian’s and quality assurance 0f compounded injections. quality assurance of Guardian's injections. In—house testing, testing, when done, utilized a done, utilized testing method called In-house a testing called QT Micro, which cannot Micro, which cannot be becausc the the test solution is be used with suspensions because test solution into sample is filtered filtered into sample media. media. Suspensions cannot be filtered. Subsequent Suspensions cannot filtered. Subsequent formulations a different formulations utilized utilized a different test test media, validation of any but n0 media, Tuff Test, Test, but no validation fills were provided provided by by Guardian. any media fills Guardian. N0 with this No quarantine was reported by this high risk sterile after high risk sterile preparation preparation after by Guardian with the Drug and Act Security the Quality Security (DQSA), safety before Quality adds to to patient patient safety (DQSA), which adds before outside outside lab testing is lab testing is completed. completed. VIII. VIII. The poloxamer concentration concentration was 5-10 times times higher formulation. higher than than patented patented formulation. Concentrations of of 6% and 12% were were used used in in the the Guardian Concentrations Guardian formulations (Imprimis’ formulations (Imprimis' utilizes poloxamer less than 3%). formulation utilizes less than This is is a 3%). This a significantly higher significantly higher concentration of ‘double sonication' 0f this this excipient. excipient. Sonication Sonication and 'double sonication’ was concentration was used used resulting resulting Guardian’s in changes noted in of viscosity, noted in emails, which which ofviscosity, in Guardian's formulation formulation changes changes and and emails, result in in known degradation degradation of 0f components. can result components. Plaintiffs' Notice of Filing Expert Reports - Page 28 of 70 IX. Particle Size Distribution was not not tested 0r analyzed Particle Size Distribution tested or by Guardian to dispensing analyzed by Guardian prior prior t0 dispensing to KeyKey-Whitman. formulation has has 98% of to Whitman. Imprimis’ Imprimis' formulation its triamcinolone triamcinolone acetonide of its acetonide particles less than 5 5 microns, confirms their microns, which confirms particles less than involved and their involved and tested tested pharmaceutical for reliable reliable and reproducible pharmaceutical process which allows for reproducible injection injection and and 0f the the actives actives during injection. injection. In In addition, dispersion of addition, sonication of poloxamer sonication 0f poloxamer above above concentrations of 5% has shown in research studies concentrations has in research to degrade studies t0 degrade into into toxic toxic products. products. Poloxamer concentrations above 5% also also form bioadhesive to bioadhesive gels gels when exposed exposed t0 resulting in in gel gel expansion and a a depot body temperature, resulting depot effect the gel wherever it effect off offthe gel wherever in the ocular space adheres in the ocular space after after injection. injection. it X. Imprimis’ patented patented injection injection formulation, Conclusions: Unlike Imprimis' with aa formulation, II believe believe with is is dangerous to the human eye, t0 the has potential to cause potential to damage and was cause ocular ocular damage eye, has and was improperly improperly compounded. reasonably reasonably degree of pharmaceutical pharmaceutical certainty, Guardian's formulation formulation that Guardian’s certainty, that injection is is demonstrably difficult to prepare. Compounding Compounding This ocular injection t0 prepare. demonstrably difficult is not available, patented drugs is commercially available, not allowed allowed by the FDA compliance compliance policy by the policy guide and Good Compounding Practices. This guide by Practices. This formulation formulation is by is a a sophisticated sophisticated multistep preparation, delivery system involving complex, multistep potential preparation, with with significant significant potential for error. specialized, highly trained and knowledgeable professionals for error. Only specialized, highly trained professionals should Should be injection, following very be preparing the the injection, strict procedures. Guardian's untested strict procedures. Guardian’s untested very outside the the scope ofUSP injection was prepared outside 0f USP 797 and and standard standard of 0f care. care. Finally, it Finally, it IACP’s violates ethics where compounders compoundcrs should violates IACP's code of ethics should not not be be compounding compounding outside their outside their scope scope of expertise. 0f expertise. for providing me with the opportunity t0 review this with the will be Thank you for opportunity to this matter. matter. IIwill be pleased pleased to t0 assist in assist the future in the future as as may be be necessary. necessary. Very Very truly yours, truly yours, QM AW Scott Karolchyk, John Scott Karolchyk, MS, RPh, RPh, FIACP Plaintiffs' Notice of Filing Expert Reports - Page 29 of 70