Strategies for Setting Patient-Centric Commercial Specifications for Biotherapeutic Products.

Commercial specifications for a new biotherapeutic product are a critical component of the product's overall control strategy that ensures safety and efficacy. This paper describes strategies for setting commercial specifications as proposed by a consortium of industry development scientists. The specifications for some attributes are guided by compendia and regulatory guidance.

Expectations for Phase-Appropriate Drug Substance and Drug Product Specifications for Early-Stage Protein Therapeutics.

Early-phase specifications are established to ensure that materials used in clinical studies have appropriate product quality, reducing the risk of harm to patients. Currently, guidance is available for specification setting practices at commercial phase. With very limited data and manufacturing experience available, it is not possible to fully align to these expectations at the start of clinical trials.

Inherent antibacterial activity of a peptide-based beta-hairpin hydrogel.

Among several important considerations for implantation of a biomaterial, a main concern is the introduction of infection. We have designed a hydrogel scaffold from the self-assembling peptide, MAX1, for tissue regeneration applications whose surface exhibits inherent antibacterial activity. In experiments where MAX1 gels are challenged with bacterial solutions ranging in concentrations from 2 x 10(3) colony forming units (CFUs)/dm2 to 2 x 10(9) CFUs/dm2, gel surfaces exhibit broad-spectrum antibacterial activity.

Cytocompatibility of self-assembled beta-hairpin peptide hydrogel surfaces.

MAX1 is a 20 amino acid peptide that undergoes triggered self-assembly to form a rigid hydrogel. When dissolved in aqueous solutions, this peptide exists in an ensemble of random coil conformations rendering it fully soluble. The addition of an exogenous stimulus results in peptide folding into beta-hairpin conformation.

Thermally reversible hydrogels via intramolecular folding and consequent self-assembly of a de novo designed peptide.

A small de novo designed peptide (MAX3) is described that exhibits complete thermoreversible self-assembly into a hydrogel network. Importantly, a prerequisite to hydrogelation is that the peptide must first fold into a conformation conducive to self-assembly. At ambient temperature, MAX3 is unfolded, resulting in a low viscosity aqueous solution.

Design and application of basic amino acids displaying enhanced hydrophobicity.

Three noncoding basic amino acids, mono-, di-, and trimethyldiaminopropionic acid (mmdap, dmdap, and tmdap), have been synthesized for use in protein design. Covalent modification of a diaminopropionic acid (dap) side chain with an increasing number of methyl moieties results in a family of residues displaying short basic side chains with varying degrees of enhanced hydrophobic character. These residues may be used to introduce charged/polar interactions into the confining hydrophobic interior or interfacial spaces of proteins.

Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide.

A general peptide design is presented that links the pH-dependent intramolecular folding of beta-hairpin peptides to their propensity to self-assemble, affording hydrogels rich in beta-sheet. Chemical responsiveness has been specifically engineered into the material by linking intramolecular folding to changes in solution pH, and mechanical responsiveness, by linking hydrogelation to self-assembly. Circular dichroic and infrared spectroscopies show that at low pH individual peptides are unstructured, affording a low-viscosity aqueous solution.