Challenge:

Client need to develop an assay to quantify a trace level impurity in a drug product.  The impurity, a positively charged quaternary salt, had no UV absorbance and required a 0.05% LOQ. Further complicating the analysis was the presence of an excess of a positively charged excipient.

QTI Solution:

QTI developed a solid phase extraction scheme to separate the cationic interference from the impurity based on its marginal hydrophobicity. A novel elution system for ion chromatography allowed quantitation in the ppm target range.

Result:

QTI generated a validated method meeting turnaround criteria and regulatory requirements.

Challenge:

Production of a biomolecule at a manufacturing facility was temporarily suspended to determine the source of a contaminate seen by HPLC at random sampling points along a production sequence. The sequence contained 63 vials representing different sequential testing points. The contaminate was only observed in random sample vials and at varying levels in each of these vials. An investigation at the plant could not determine the source or identity of the contaminate.

QTI Solution:

QTI was initially contacted to isolate sufficient quantities of the contaminate from the sample vials to allow identification by MS and NMR. After a review of the history of the project and discussions with the client, QTI recommended an investigation of the sampling technique to determine the contaminate source.

Result:

Noting that the only common thread throughout production sequence sampling was the sample vials themselves, QTI recommended an extraction study of the sample vial as individual vial components. Using the placebo solution as the extraction solvent, QTI determined that the source of the contaminate was the sample vial O-ring.  Since the source of the contaminate was not related to the production sequence, manufacturing could continue.

Challenge:

Client recently received approval for the generic equivalent of a major US prescription product. In-house laboratory did not have the capacity to handle the release testing for the large number of batches manufactured each month

QTI Solution:

Five analytical methods were quickly transferred to be performed in our laboratories.

Result:

Client's requirement for release results within 10 days of manufacture allowed them to meet their customer demands for the new source of product and gain market share.

Challenge:

Client provided QTI with an API from a foreign contract manufacturer.  The client wanted to confirm the contract manufacturer’s residual solvent analysis.

QTI Solution:

QTI screened the API for residual solvents using both the contract manufacturer’s method and an in-house procedure that elutes 23 common residual solvents. QTI’s method identified an unknown peak, not seen with the manufacturer’s method, which was identified by GC-MS and confirmed by direct chromatographic comparison against a standard.

Result:

Client rejected the batch and tighter controls were placed on the API batch testing.

Challenge:

QTI was contracted to determine the controlled extractables from the raw materials and molded components of a dry powder inhaler (DPI) device.

QTI Solution:

QTI developing LC-MS and GC-MS chromatographic methods for organic extractables (known antioxidants, oligomers, and possible unknown organic extractables) and ICP-OES for unknown inorganic extractables.

Result:

The chromatographic methods detected the known antioxidant and its oxidation product, an unknown antioxidant which was tentatively identified by MS and confirmed with an authentic material, and expected oligomers. The ICP analysis detected measurable amounts of three elements.

The results of the controlled extractables study indicated that a single GC-FID procedure would be applicable for routine extractable determinations. QTI developed and validated the GC-FID procedure for the two antioxidants, the oxidation product, and resin oligomers. This method is in current use for generating an extractables Certificate of Analysis for each lot of resin raw material. There was no routine testing for inorganic extractables as the three detected elements were at trace levels and were excipient components of the drug formulation. 

Challenge:

A client was required to evaluate the leachable metals from a metered dose inhaler (MDI) product because of a change in the formulation. Client in-house analyses showed unexpectedly high levels of the metal canister elements and QTI was contracted to confirm the in-house results.

QTI Solution:

The client had developed a cutting procedure for opening the MDI canister that was used for quantitative removal of the canister contents for potency and purity analysis of actives. This procedure was not applicable for leachable metals testing since the act of opening the canister contaminated the sample with very high levels of metal ions. QTI designed and had built an automated sample preparation unit that completed discharged up to 36 MDIs through the valve into separate high density polyethylene (HDPE) bottles. This procedure allowed complete analysis of extractable metals without contamination from the sample preparation procedure.

Result:

The levels of extractable metal ions from the MDI was actually much lower than the in-house testing showed and the product passed stability testing.

Challenge:

Client had a deadline for an NDA submission with the FDA.  The stability samples, which were manufactured outside of the USA, were retained by customs for two months which delayed the initiation of the stability study.  The client wanted to keep aggressive timelines to maintain the NDA submission date.

QTI Solution:

QTI worked compressed testing timelines for the last stability pull prior to FDA submission.  The samples were tested, reviewed, QA released, and reported to the client in a two week timeframe.

Result:

Client received the data within the compressed timeline and the reports were submitted to the FDA on time.

Challenge:

A client had developed an innovative medicated implant for sustained drug release.  A method was needed to provide research support of various formulation to monitor the drug release profile.

QTI Solution:

QTI developed a novel product support and modified a USP dissolution procedure to monitor drug release over multiple days.

Result:

The client was able to modify the formation to tailor specific drug release profiles.

Challenge:

A multinational pharmaceutical client required that an experimental API that needed special storage and handling conditions be made available for worldwide distribution to corporate research facilities.  However, because of safety constraints, the Client did not have capability for storage and distribution of the quantities necessary.

QTI Solution:

QTI put systems and processes in place to safely store, handle and distribute the material on an as needed basis.

Result:

QTI is able provide material on request to any worldwide destination within 2 days.